1. Polymeric micelles for MCL-1 gene silencing in breast tumors following systemic administration.
- Author
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Garg SM, Falamarzian A, Vakili MR, Aliabadi HM, Uludağ H, and Lavasanifar A
- Subjects
- Animals, Breast metabolism, Breast pathology, Breast Neoplasms genetics, Breast Neoplasms pathology, Female, Humans, Mice, Nude, RNA Interference, RNA, Small Interfering genetics, RNA, Small Interfering therapeutic use, Spermine analogs & derivatives, Transfection methods, Breast Neoplasms therapy, Caproates chemistry, Lactones chemistry, Micelles, Myeloid Cell Leukemia Sequence 1 Protein genetics, Polyethylene Glycols chemistry, RNA, Small Interfering administration & dosage, RNAi Therapeutics methods
- Abstract
Aim: To develop delivery systems for efficient siRNA delivery to breast cancer., Methods: Poly(ethylene oxide)-block-poly(ϵ-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 MCL-1 siRNA in tumor upon intravenous administration., Conclusion: RGD4C-PEO-b-P(CL-g-SP) micelles, without or with cholesterol modification, can provide efficient delivery of siRNA to breast tumors following systemic administration.
- Published
- 2016
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