Polymeric micelles for MCL-1 gene silencing in breast tumors following systemic administration.

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.