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

• Published in: Journal of materials science Vol. 53; no. 2; pp. 892 - 907
• Main Authors: Ma, Xiaoqian, Shi, Xiaoxiao, Bai, Shuang, Gao, Yong-E, Hou, Meili, Han, Man-Yi, Xu, Zhigang
• Format: Journal Article
• Language: English
• Published: New York Springer US 2018; Springer; Springer Nature B.V
• Subjects: Aqueous solutions; Biomaterials; Blood circulation; Blood vessels; Characterization and Evaluation of Materials; Chemistry and Materials Science; Classical Mechanics; Crystallography and Scattering Methods; Cytotoxicity; Doxorubicin; Drug delivery systems; Drugs; Folic acid; Health aspects; Loading rate; Materials Science; Micelles; Organic chemistry; Polymer Sciences; Side effects; Solid Mechanics; Stimuli; Toxicity; Tumors; Vehicles; Polymeric Prodrugs; RAFT Agent; Nanosized Drug Carriers (NSDCs); Micellar Stability; High Drug Loading
• ISSN: 0022-2461; 1573-4803
• DOI: 10.1007/s10853-017-1546-z

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.