In this study, a series of conjugates were designed and synthesized by fusing the SMAC peptide and P1 target peptide, and coupling with CPT, with the hope that they can play a synergistic role in promoting cell apoptosis. The in vitro anti-tumor activity study found that the better conjugate 4 had the best activity on HER2-positive cells, while it was less toxic to HER2-negative cells. From the experimental results, the coupling position of CPT affected the activity of the conjugates. Conjugates 1, 4 and 7, which connected the load in the same way, had different inhibitory activities on three HER2-positive cells, and among them, conjugate 4 showed the best activity. We speculated it is related to the releasing efficiency of free SMAC peptide and CPT. The subsequent biological activity evaluations of conjugate 4 confirmed that the introduction of the SMAC peptide sequence can enhance the activity of Caspase 3 and indeed play a role in promoting apoptosis. Conjugate 4 reduced the expression of XIAP and cIAP1 in SK-BR-3 cells in a concentration dependent manner. The in vivo activity study also fully proved that the antitumor activity as well as safety of conjugate 4 was superior to CPT. The pro-apoptotic effect of conjugate 4 is significantly superior to the C4 group without fused SMAC peptide and the C4+SMAC combination drug group. This indicates that that the introduced SMAC peptide exerts a synergistic anti-tumor effect. When CPT is engineered into PDCs molecules, its in vitro activity related to CPT can be retained but is somewhat diminished. This attenuation may be attributed to the fact that PDCs must undergo cellular internalization and release of CPT or its derivatives in the intracellular environment to exert anti-tumor activity.

In this study, a series of conjugates were designed and synthesized by fusing the SMAC peptide and P1 target peptide, and coupling with CPT, with the hope that they can play a synergistic role in promoting cell apoptosis. The in vitro anti-tumor activity study found that the better conjugate 4 had the best activity on HER2-positive cells, while it was less toxic to HER2-negative cells. From the experimental results, the coupling position of CPT affected the activity of the conjugates. Conjugates 1, 4 and 7, which connected the load in the same way, had different inhibitory activities on three HER2-positive cells, and among them, conjugate 4 showed the best activity. We speculated it is related to the releasing efficiency of free SMAC peptide and CPT. The subsequent biological activity evaluations of conjugate 4 confirmed that the introduction of the SMAC peptide sequence can enhance the activity of Caspase 3 and indeed play a role in promoting apoptosis. Conjugate 4 reduced the expression of XIAP and cIAP1 in SK-BR-3 cells in a concentration dependent manner. The in vivo activity study also fully proved that the antitumor activity as well as safety of conjugate 4 was superior to CPT. The pro-apoptotic effect of conjugate 4 is significantly superior to the C4 group without fused SMAC peptide and the C4+SMAC combination drug group. This indicates that that the introduced SMAC peptide exerts a synergistic anti-tumor effect. When CPT is engineered into PDCs molecules, its in vitro activity related to CPT can be retained but is somewhat diminished. This attenuation may be attributed to the fact that PDCs must undergo cellular internalization and release of CPT or its derivatives in the intracellular environment to exert anti-tumor activity.

In this study, a series of conjugates were designed and synthesized by fusing the SMAC peptide and P1 target peptide, and coupling with CPT, with the hope that they can play a synergistic role in promoting cell apoptosis. The in vitro anti-tumor activity study found that the better conjugate 4 had the best activity on HER2-positive cells, while it was less toxic to HER2-negative cells. From the experimental results, the coupling position of CPT affected the activity of the conjugates. Conjugates 1, 4 and 7, which connected the load in the same way, had different inhibitory activities on three HER2-positive cells, and among them, conjugate 4 showed the best activity. We speculated it is related to the releasing efficiency of free SMAC peptide and CPT. The subsequent biological activity evaluations of conjugate 4 confirmed that the introduction of the SMAC peptide sequence can enhance the activity of Caspase 3 and indeed play a role in promoting apoptosis. Conjugate 4 reduced the expression of XIAP and cIAP1 in SK-BR-3 cells in a concentration dependent manner. The in vivo activity study also fully proved that the antitumor activity as well as safety of conjugate 4 was superior to CPT. The pro-apoptotic effect of conjugate 4 is significantly superior to the C4 group without fused SMAC peptide and the C4+SMAC combination drug group. This indicates that that the introduced SMAC peptide exerts a synergistic anti-tumor effect. When CPT is engineered into PDCs molecules, its in vitro activity related to CPT can be retained but is somewhat diminished. This attenuation may be attributed to the fact that PDCs must undergo cellular internalization and release of CPT or its derivatives in the intracellular environment to exert anti-tumor activity.

In this study, a series of conjugates were designed and synthesized by fusing the SMAC peptide and P1 target peptide, and coupling with CPT, with the hope that they can play a synergistic role in promoting cell apoptosis. The in vitro anti-tumor activity study found that the better conjugate 4 had the best activity on HER2-positive cells, while it was less toxic to HER2-negative cells. From the experimental results, the coupling position of CPT affected the activity of the conjugates. Conjugates 1, 4 and 7, which connected the load in the same way, had different inhibitory activities on three HER2-positive cells, and among them, conjugate 4 showed the best activity. We speculated it is related to the releasing efficiency of free SMAC peptide and CPT. The subsequent biological activity evaluations of conjugate 4 confirmed that the introduction of the SMAC peptide sequence can enhance the activity of Caspase 3 and indeed play a role in promoting apoptosis. Conjugate 4 reduced the expression of XIAP and cIAP1 in SK-BR-3 cells in a concentration dependent manner. The in vivo activity study also fully proved that the antitumor activity as well as safety of conjugate 4 was superior to CPT. The pro-apoptotic effect of conjugate 4 is significantly superior to the C4 group without fused SMAC peptide and the C4+SMAC combination drug group. This indicates that that the introduced SMAC peptide exerts a synergistic anti-tumor effect. When CPT is engineered into PDCs molecules, its in vitro activity related to CPT can be retained but is somewhat diminished. This attenuation may be attributed to the fact that PDCs must undergo cellular internalization and release of CPT or its derivatives in the intracellular environment to exert anti-tumor activity.

In this study, a series of conjugates were designed and synthesized by fusing the SMAC peptide and P1 target peptide, and coupling with CPT, with the hope that they can play a synergistic role in promoting cell apoptosis. The in vitro anti-tumor activity study found that the better conjugate 4 had the best activity on HER2-positive cells, while it was less toxic to HER2-negative cells. From the experimental results, the coupling position of CPT affected the activity of the conjugates. Conjugates 1, 4 and 7, which connected the load in the same way, had different inhibitory activities on three HER2-positive cells, and among them, conjugate 4 showed the best activity. We speculated it is related to the releasing efficiency of free SMAC peptide and CPT. The subsequent biological activity evaluations of conjugate 4 confirmed that the introduction of the SMAC peptide sequence can enhance the activity of Caspase 3 and indeed play a role in promoting apoptosis. Conjugate 4 reduced the expression of XIAP and cIAP1 in SK-BR-3 cells in a concentration dependent manner. The in vivo activity study also fully proved that the antitumor activity as well as safety of conjugate 4 was superior to CPT. The pro-apoptotic effect of conjugate 4 is significantly superior to the C4 group without fused SMAC peptide and the C4+SMAC combination drug group. This indicates that that the introduced SMAC peptide exerts a synergistic anti-tumor effect. When CPT is engineered into PDCs molecules, its in vitro activity related to CPT can be retained but is somewhat diminished. This attenuation may be attributed to the fact that PDCs must undergo cellular internalization and release of CPT or its derivatives in the intracellular environment to exert anti-tumor activity.