Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficac...Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.展开更多
The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymer...The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.展开更多
基金supported by National Natural Science Foundation of China (No. 51373168)
文摘Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.
基金National Key Technologies R&D Program for New Drugs(Grant No.2009ZX09301-002,2009ZX09304-004).
文摘The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.
