Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solu...Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(No.21576029)National Key R&D Program of China(No.2017YFD0601205).
文摘Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.
