期刊
BIOMATERIALS
卷 129, 期 -, 页码 83-97出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.03.020
关键词
Nanomedicine; Organic-inorganic hybrid materials; siRNA; Drug delivery; Chemotherapy
资金
- Hong Kong Research Grants Council (RGC) [11301215]
- National Basic Research Program of China (973 Program) [2014CB931901]
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-gamma-cyclodextrin (PC) through the supra molecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes. The PCD/siRNA nanocomplex is further decorated with the exterior neodymium (Nd)-integrated PC (Nd-PC) layer to obtain the PCD/siRNA/Nd-PC nanoassembly in which the interior PC serves as an efficient carrier for simultaneous delivery of Dox and siRNA to the human breast cancer cell line, Dox-resistant MCF-7 (MCF-7/ADR) both in vitro and in vivo. The exterior Nd-PC layer improves the drug sensitivity to the MCF-7/ADR cells as a result of the improved nanoassembly uptake, reduced drug efflux, and enhanced apoptosis, as evidenced by multiple regulation of a series of intracellular proteins related to MDR. Furthermore, in vivo delivery of the PCD/siRNA/Nd-PC nanoassembly is demonstrated to inhibit tumor growth in the mouse model with MCF-7/ADR tumor xenografts as a result of reduced angiogenesis and increased necrosis at the tumor site. This study reveals a simple and universal strategy to transform polymer-based nanoassemblies into advanced organic-inorganic nanotherapeutics suitable for cancer MDR therapy. (C) 2017 Elsevier Ltd. All rights reserved.
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