title: Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid.
abstract: In order to enhance the in vivo codelivery efficiency of gambogic acid (GA) and all-trans retinoic acid (ATRA), our strategy was to entrap GA in the self-assembled nanoparticles based on amphiphilic hyaluronic acid (HA)-ATRA (HRA) conjugate. In this way, GA and ATRA were loaded simultaneously in a nanocarrier and codelivered into the tumor cell through HA receptor-mediated endocytosis. GA-loaded HRA nanoparticles (GA-HRA) were prepared by a dialysis method, and their physicochemical characteristics were investigated as well. GA-HRA exhibited a high drug loading capacity (31.1%), had a particle size in the range of 100-150 nm, and good biocompatibility. HRA nanoparticles were effectively internalized by MCF-7 cells and translocated into the nucleus in a time-dependent manner. The in vivo imaging analysis demonstrated that the fluorescent signals in the tumor were markedly increased with DiR-loaded nanoparticles after intravenous administration compared to free DiR solution, suggesting it has excellent tumor targeting properties. More importantly, GA-HRA exhibited excellent in vivo efficacy with dramatically reduced toxicity. In conclusion, with the assistance of HRA nanoparticles, GA and ATRA can successfully realize an effective combination chemotherapy as well as tumor-targeted delivery.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yuanke
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Fatima Zohra
authors.initials: FZ
authors.lastname: Dahmani
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Hongpan
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D014018:Tissue Distribution; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004338:Drug Combinations; D044004:Xanthones; D014212:Tretinoin; C052659:gambogic acid; D006820:Hyaluronic Acid
keywords: hyaluronic acid; nanoparticles; tumor targeting