A series of well-defined amphiphilic linear-dendritic block copolymers （telodendrimers, MPEG-b-PAMAM-cholesterol） with 1,2,4 or 8 cholesteryl groups （named as P1, P2, P4, P8, respectively） were synthesized. Their ...A series of well-defined amphiphilic linear-dendritic block copolymers （telodendrimers, MPEG-b-PAMAM-cholesterol） with 1,2,4 or 8 cholesteryl groups （named as P1, P2, P4, P8, respectively） were synthesized. Their chemical structures were char- acterized with IH NMR and mass spectrum （MALDI-TOF MS）. The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin （DOX） and paclitaxel （PTX） for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is in- creased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counter- parts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles （NPs） of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements （DLS） and transmission electron microscope （TEM）. In vitro drug release experiment demonstrated that P8 ex- hibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxi- city experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug （DOX or PTX）. This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.展开更多
Amphiphilic dendritic poly（glutarnic acid）-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly（glutamic acid） as the macroinitiator in the ring-opening polymerization of NCA-Phe. The ...Amphiphilic dendritic poly（glutarnic acid）-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly（glutamic acid） as the macroinitiator in the ring-opening polymerization of NCA-Phe. The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly（glutamic acid） segments as shell. The biocompatibility of the micelles was studied. The release of the anticancer drug doxorubicin from the micelles was investigated in vitro. The results showed that the sustaining release of the drug could last for 60 h. The micellar drug release system was efficient in inhibiting the proliferation of HepG2 liver cancer cells, 75% cancer cells were killed under appropriate in vitro incubation.展开更多
基金support from the National Natural Science Foundation of China(51233004,51273196,51203153,51021003 and 51303174)the Ministry of Science and Technology of China(international cooperation program 2011DFR51090)Jilin province science and technology development program(20130521011JH)
文摘A series of well-defined amphiphilic linear-dendritic block copolymers （telodendrimers, MPEG-b-PAMAM-cholesterol） with 1,2,4 or 8 cholesteryl groups （named as P1, P2, P4, P8, respectively） were synthesized. Their chemical structures were char- acterized with IH NMR and mass spectrum （MALDI-TOF MS）. The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin （DOX） and paclitaxel （PTX） for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is in- creased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counter- parts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles （NPs） of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements （DLS） and transmission electron microscope （TEM）. In vitro drug release experiment demonstrated that P8 ex- hibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxi- city experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug （DOX or PTX）. This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.
基金supported by the National Basic Research Program of China (973 Program,2011CB606206)National High-Tech Research & Development Program of China (863 Program,2007AA021801)+2 种基金National Natural Science Foundation of China (50633020 & 50830105)Sichuan Youth Science & Technology Foundation (07ZQ026-013)Open Fund of Engineering Research Center of Biomass Materials,Ministry of Education (2010LF4002)
文摘Amphiphilic dendritic poly（glutarnic acid）-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly（glutamic acid） as the macroinitiator in the ring-opening polymerization of NCA-Phe. The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly（glutamic acid） segments as shell. The biocompatibility of the micelles was studied. The release of the anticancer drug doxorubicin from the micelles was investigated in vitro. The results showed that the sustaining release of the drug could last for 60 h. The micellar drug release system was efficient in inhibiting the proliferation of HepG2 liver cancer cells, 75% cancer cells were killed under appropriate in vitro incubation.
