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Acid-activatable doxorubicin prodrug micelles with folate-targeted and ultra-high drug loading features for efficient antitumor drug delivery

Ma, Xiaoqian, Shi, Xiaoxiao, Bai, Shuang, Gao, Yong-E, Hou, Meili, Han, Man-Yi, Xu, Zhigang
Journal of materials science 2018 v.53 no.2 pp. 892-907
aqueous solutions, blood circulation, chemical structure, cytotoxicity, doxorubicin, folic acid, micelles, nanomedicine, neoplasm cells, neoplasms, surfactants, therapeutics
Stimuli-responsive nanomedicine shows high therapeutic effects and low side effects to tumor cells and tissues, representing a preferable therapeutics for cancer therapy. Herein, we design an acid-stimuli-responsive doxorubicin polymeric prodrug (OM@DOX), and this amphiphilic prodrug has a unique chemical structure with prominent advantages, including high drug loading rate (as high as 61.5 wt%), pH-triggered drug release and targeted access to cells. This smart polymeric prodrug has a preferable size of ~40 nm and strong micellar stability in aqueous solution, which is benefited to the long blood circulation and efficient extravasation from tumor vessel. Moreover, the prodrug micelles showed a higher cytotoxicity against tumor cells (HeLa cells) than normal cells (L929 cells), likely suggesting the potential tumor-specific targeting ability. To render this prodrug micelles with targeting function, folic acid (FA) molecules conjugated prodrug (FA-OM@DOX) further showed selectively higher cytotoxicity to KB tumor cells (FA-receptor-positive) than A549 tumor cells (FA-receptor-negative). Considering the rapidly cell-penetrating ability and aforementioned features, we believe that the present prodrug strategy has the potential as a promising nanomedicine and providing inspired insights to design multifunctional drug delivery nanoplatforms.