期刊
NANOMEDICINE
卷 11, 期 17, 页码 2319-2339出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2016-0178
关键词
cancer; cholesterol; MCL-1; MDA-MB-435; PEO-b-PCL; polymeric micelles; RGD4C; siRNA delivery; spermine
资金
- Canadian Institute of health Research (CIHR) [MOP 137153]
- Alberta Innovates Health Solutions (AIHS)
- ACF
- JN Tata Trust
Aim: To develop delivery systems for efficient siRNA delivery to breast cancer. Methods: Poly(ethylene oxide)-block-poly(e-caprolactone-grafted-spermine) (PEO-b-P(CL-g-SP)) micelles were modified with cholesterol group in their core and with RGD4C peptide on their shell. Transfection efficiency of complexed MCL-1 siRNA in MDA-MB-435 was investigated, in vitro and in vivo following intratumoral and intravenous injection. Results: Cholesteryl modification of the core significantly increased the transfection efficiency of PEO-b-P(CL-g-SP)-complexed siRNA, in vitro, but not following intratumoral or intravenous administration, in vivo. Instead, RGD4C modification of the micellar shell enhanced transfection efficiency of complexed MCL1 siRNA in tumor upon intravenous administration. Conclusion: RGD4C-PEO-b-P(CL-gSP) micelles, without or with cholesterol modification, can provide efficient delivery of siRNA to breast tumors following systemic administration.
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