General Information of This Peptide
Peptide ID
PEP00625
Peptide Name
Lytic peptides 6
Sequence
LVRRFRRFFRRLRRCVLL
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
FA-P7-PTX [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
0.00%
Administration Time 4 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
16.70%
Administration Time 6 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
38.90%
Administration Time 8 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
50.00%
Administration Time 10 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
63.00%
Administration Time 12 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
65.20%
Administration Time 16 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 7 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
66.90%
Administration Time 14 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
67.30%
Administration Time 18 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Experiment 9 Reporting the Activity Data of This PDC [1]
Indication Hepatoma
Efficacy Data Tumor growth inhibition value (TGI)
69.10%
Administration Time 20 days
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
To study the anticancer activity of FA-P7-PTX in vivo, we performed tumor-bearing mice model with H22cells by administering once every two days peritumoral injection of FA-P7-PTX (12 μmol/kg), PTX (12 μmol/kg, as the positive control), or 0.9% saline as the negative control for 2 weeks. Compared with control group, the tumor volumes of the FA-P7-PTX group were dramatically reduced by 69% with no significant variation in mouse body weight. Meanwhile FA-P7-PTX exhibited stronger inhibitory effects on tumor volume compared with PTX (69% versus 49%). The result confirmed that FA-P7-PTX possessed higher potency in slowing the growth of solid tumors.

   Click to Show/Hide
In Vivo Model Tumor-bearing mice model with H22 cells.
In Vitro Model Hepatoma H22 cell CVCL_H613
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Invasive breast carcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
1.39 ± 0.12 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Ovarian endometrioid adenocarcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
1.42 ± 0.08 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

   Click to Show/Hide
In Vitro Model Ovarian endometrioid adenocarcinoma A2780 cell CVCL_0134
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Invasive ductal carcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
2.92 ± 0.2 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

   Click to Show/Hide
In Vitro Model Invasive ductal carcinoma MCF7/PTX cell CVCL_C5RS
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Chronic myeloid leukemia
Efficacy Data Half maximal inhibitory concentration (IC50)
3.85 ± 0.9 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

   Click to Show/Hide
In Vitro Model Chronic myeloid leukemia K562 cell CVCL_0004
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Ovarian serous cystadenocarcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
5.49 ± 0.36 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cell CVCL_0532
Experiment 6 Reporting the Activity Data of This PDC [1]
Efficacy Data Half maximal inhibitory concentration (IC50)
45.21 ± 1.79 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

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Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Normal Human umbilical vein endothelial cells Homo sapiens
Lytic peptides 6 - Paclitaxel conjugate [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Invasive breast carcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
1.98 ± 0.14 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

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Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Ovarian endometrioid adenocarcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
2.79 ± 0.17 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Ovarian endometrioid adenocarcinoma A2780 cell CVCL_0134
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Chronic myeloid leukemia
Efficacy Data Half maximal inhibitory concentration (IC50)
3.82 ± 0.29 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Chronic myeloid leukemia K562 cell CVCL_0004
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Invasive ductal carcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
5.53 ± 0.76 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Invasive ductal carcinoma MCF7/PTX cell CVCL_C5RS
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Ovarian serous cystadenocarcinoma
Efficacy Data Half maximal inhibitory concentration (IC50)
6.61 ± 0.94 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

   Click to Show/Hide
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cell CVCL_0532
Experiment 6 Reporting the Activity Data of This PDC [1]
Efficacy Data Half maximal inhibitory concentration (IC50)
37.22 ± 2.36 μM
Administration Time 48 h
Evaluation Method MTT assay
MOA of PDC
We have previously reported that structural optimized lytic peptides I-3 and I-7 can be used as cell-disrupting peptides and molecular carriers. Meanwhile, PTX, a firstline antitumor drug, its poor aqueous solubility (no more than 0.004mg/mL) and acquired drug resistant need to be addressed urgently. In this work, we choose the 16-site cysteine-substituted I-3 and I-7 (namely P3 and P7, respectively) served as peptide backbone and we designed a novel folate targeting peptide-PTX conjugates to achieve selective tumor delivery, enhance cellular uptake, make FA-P3/P7-PTX conjugates water-soluble and overcome drug resistance. The conjugates were evaluated for the antiproliferative activity in different cancer cell lines, the inhibitory rate of tubulin polymerization, hemolytic toxicity and water solubility. Furthermore, we assessed the conjugates for their cellular uptake, Membrane permeability, pro-apoptosis, alternation of mitochondrial membrane potential, rat plasma stability and cell apoptosis pathway in PTX resistant MCF-7/PTX cells. Finally, we researched the most optimized conjugate in vivo antitumor efficacy compared with free PTX.

   Click to Show/Hide
Description
The anticancer activities of the conjugates were evaluated using various cancer cells (MCF-7, MCF-7/PTX, K562, A2780 and SKOV3). The IC50 values are listed in Table 3, and PTX was used for comparison. All the conjugates exhibited improved cytotoxic effects on various cancer cells. According to the results, all the conjugates showed significantly stronger antiproliferative activity than former lytic peptides (P3 and P7), and FA-P3-PTX and FA-P7-PTX showed more excellent antiproliferative activity than P3-PTX and P7-PTX in FA-overexpressing cancer cells MCF-7 (1.79 μM versus 2.15 μM; 1.39 μM versus 1.98 μM), MCF-7/PTX (4.54 μM versus 6.11 μM; 2.92 μM versus 5.53 μM), A2780 (1.95 μM versus 2.69 μM; 1.42 μM versus 2.79 μM), respectively. Thus, the conjugate FA-P3-PTX and FA-P7-PTX exhibited great antiproliferative activity on folate receptors overexpressing cancer cells, and almost equal potency to both drug resistant and -sensitive cells. Meanwhile, the conjugates showed weak toxicity to the normal cell lines HUVEC. To assess the safety profile of the designed conjugates, we examined their hemolytic activity using RBCs. As depicted in Fig. 1, all the tested peptides exhibited modest hemolytic activity.

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In Vitro Model Normal Human umbilical vein endothelial cells Homo sapiens
References
Ref 1 Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance. Eur J Med Chem. 2019 Jun 1;171:104-115. doi: 10.1016/j.ejmech.2019.03.031. Epub 2019 Mar 18.