The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.