Self-assembled polymer/inorganic hybrid nanovesicles for multiple drug delivery to overcome drug resistance in cancer chemotherapy.
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.
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Meng-Qing
MQ
Gong
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Jin-Long
JL
Wu
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Bin
B
Chen
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Ren-Xi
RX
Zhuo
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Si-Xue
SX
Cheng
D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple; D006367:HeLa Cells; D006801:Humans; D049329:Nanostructures / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry
D000970:Antineoplastic Agents; D011108:Polymers; D011804:Quinolines; D004317:Doxorubicin; C402343:tariquidar