title: A prodrug strategy based on chitosan for efficient intracellular anticancer drug delivery.
abstract: Doxorubicin (DOX), one of the most widely used anticancer drugs, is restricted in clinical application due to its severe side effects and inefficient cellular uptake. To overcome the drawbacks, herein, an endosomal pH-activated prodrug was designed and fabricated by conjugating DOX with chitosan via an acid-cleavable hydrazone bond. The resulting DOX conjugates can self-assemble into nano-sized particles, which were very stable and presented no burst release of DOX at a neutral pH condition. Notably, the nanoparticles exhibited excellent cell uptake properties and a remarkable drug accumulation in tumor cells. Once internalized into the cells, moreover, DOX can be fast released from the nanoparticles, and the release mechanism changed from the anomalous transport at pH 7.4 to the combination pattern of diffusion- and erosion-controlled release at pH 6.0 or 5.0. The prodrugs showed obvious cytotoxicity for HeLa cells with fairly low IC50 values, offering a new platform for targeted cancer therapy.
authors.affiliation: Center for Degradable and Flame-Retardant Polymeric Materials (ERCPM-MoE), College of Chemistry, State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), Sichuan University, 29 Wangjiang Road, Chengdu 610064, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Jiang-Ling
authors.initials: JL
authors.lastname: Zhou
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Yu-Zhong
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D053758:Nanoparticles / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D011355:Prodrugs; D004317:Doxorubicin; D048271:Chitosan