期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 467, 期 -, 页码 35-42出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2015.12.052
关键词
Drug delivery; Reduced graphene oxide; Anti-cancer drugs; Breast cancer; Poly-L-lysine; Endocytosis
资金
- National Science Foundation of China [21205097]
- National Key Basic Research Program of China (973 Program) [2013CB127804]
- Institute for Clean Energy & Advanced Materials (Southwest University, Chongqing, China)
- Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies (Chongqing, China)
- Southwest University (Chongqing, China) [SWU111071]
- Chongqing Engineering Research Center for Rapid diagnosis of Dread Disease (Chongqing, China)
- Chongqing development and reform commission (Chongqing, China)
Targeted drug delivery has become important, attractive and challenging in biomedical science and applications. Anti-HER2 antibody-conjugated poly-L-lysine functionalized reduced graphene oxide (antiHER2-rGO-PLL) nanocarriers were prepared to efficiently deliver doxorubicin targeting at the nucleus of HER2 over-expressing cancer cells. The polycationic PLL was first covalently grafted to graphene oxide (GO) nanosheets followed by reduction to obtain rGO-PLL with high drug loading and good colloidal stability. The anti-HER2 antibodies were subsequently conjugated to the amino groups of PLL to achieve excellent cell uptake capability. Cellular uptake of anti-HER2-rGO-PLL into MCF7/HER2 cells is significantly higher than that of rGO-PLL due to the specific targeting of anti-HER2 to HER2 overexpressing breast cancer cells. Additionally the anti-HER2-rGO-PLL enables a fast accumulation of DOX inside the nucleus, its subcellular site of action. In vitro cytotoxicity measurements clearly reveal a seven fold improvement in the anticancer efficacy for anti-HER2-rGO-PLL/DOX in comparison to rGO-PLL/DOX. The enhanced anticancer efficacy could be ascribed to the different intracellular DOX distributions resulted from the different internalization routes that are energy-dependent macropinocytosis and energy-independent direct penetration by anti-HER2-rGO-PLL and rGO-PLL, respectively. The results demonstrate that anti-HER2 conjugated rGO-PLL developed is a promising vehicle for efficient nuclear delivery of chemotherapeutic agents to HER2 over-expressing tumours. (C) 2016 Elsevier Inc. All rights reserved.
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