期刊
NANOTECHNOLOGY
卷 25, 期 25, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/0957-4484/25/25/255101
关键词
chitosan; Doxorubicin; prodrug; acid-activated; controlled drug release
资金
- Research Fund for the Doctoral Program of Higher Education of China [20130181120067]
- National 863 Program of China [2012AA062904]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT 1026]
- Program of International ST Cooperation [2011DFA51420]
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.
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