Inhibiting Multidrug Resistance with Transferrin-Targeted Polymersomes through Optimization of Ligand Density.
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| Abstract |
Transferrin-conjugated polymersomes, transferrin-biotin/avidin/biotin-Pluronic F127-poly(lactic acid) (Tf-F127-PLA), were successfully prepared through a biotin-avidin bridging technique to study their ability to inhibit multidrug resistance of cancer cells. Hydrophilic doxorubicin (DOX) was selected as the model drug to be loaded into Tf-F127-PLA polymersomes. DOX loaded in Tf-F127-PLA polymersomes was released fast initially, followed by a slow release. The effect of the transferrin ligand density of Tf-F127-PLA/DOX polymersomes on their targeting properties was studied by both cytotoxicity and cellular uptake assays against A549 lung cancer cells. It was shown that Tf-F127-PLA/DOX polymersomes had better targeting ability than nontargeted drug-loaded polymersomes. Furthermore, Tf-F127-PLA/DOX polymersomes with 2% Tf molar content have more effective antitumor activity and a higher cellular uptake than those with 4 and 5% Tf molar content. 2% Tf-F127-PLA/DOX polymersomes also exhibited better anticancer ability in multidrug resistant cancer cells A549/ADR than nontargeted PLA-F127-PLA/DOX polymersomes. It was further proved that the endocytosis of polymersomes by A549/ADR cells was an energy-dependent endocytosis process, which was related to clathrin, macrocytosis, and caveolin. Also, the endocytosis of Tf-F127-PLA/DOX polymersomes was proven to be mediated by the transferrin receptor.
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| Authors | Shui Ling Yi, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong |
| Journal | Langmuir : the ACS journal of surfaces and colloids (Langmuir) Vol. 39 Issue 45 Pg. 15920-15931 (11 14 2023) ISSN: 1520-5827 [Electronic] United States |
| PMID | 37922445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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