Journal
LANGMUIR
Volume 31, Issue 18, Pages 5115-5122Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.5b00542
Keywords
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Funding
- National Natural Science Foundation of China [21274113]
- Ministry of Science and Technology of China (National Basic Research Program of China) [2011CB606202]
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With the aim to develop a facile strategy to prepare functional drug carriers to overcome multidrug resistance (MDR), we prepared heparin/protamine/calcium carbonate (HP/PS/CaCO3) hybrid nanovesicles with enhanced cell internalization, good serum stability, and pH sensitivity for drug delivery. All the functional components including protamine to improve the cell uptake, heparin to enhance the stability, and CaCO3 to improve drug loading and endow the system with pH sensitivity were introduced to the nanovesicles by self-assembly in an aqueous medium. An antitumor drug (doxorubicin, DOX) and a drug resistance inhibitor (tariquidar, TQR) were coloaded in the nanovesicles during self-assembly preparation of the nanovesicles. The drug loaded nanovesicles, which had a mean size less than 200 nm, exhibited a pH-sensitive drug release behavior. In vitro study was carried out in both nonresistant cells (HeLa and MCF-7) and drug-resistant cancer cells (MCF-7/ADR). Because of the enhanced intracellular and nuclear drug accumulation through effective inhibition of the P-gp efflux transporter, DOX/TQR coloaded nanovesicles showed significantly improved tumor cell inhibitory efficiency, especially for drug-resistant cells. These results suggest the self-assembled nanovesicles have promising applications in multidrug delivery to overcome drug resistance in tumor treatments.
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