Dendron-Polymer Conjugate Based Cross-Linked Micelles: A Robust and Versatile Nanosystem for Targeted Delivery

Bioconjugate Chemistry
Filiz CalikRana Sanyal

Abstract

Among various nanomedicine platforms, biodegradable polymeric micelles offer a viable approach to targeted cancer therapy. Herein, we report fabrication of core-cross-linked micelles using dendron-polymer conjugates as building blocks. Hydrophobic polyester dendrons containing peripheral alkene groups are conjugated to a hydrophilic poly(ethylene glycol) based copolymer bearing activated ester groups for appending an amine-containing peptide based targeting group, namely, cRGDfK. Micellar constructs assembled in aqueous media were cross-linked using a tetra-thiol molecule via the photochemical thiol-ene reaction. Cross-linked and non-cross-linked micelles were compared in terms of their critical micellar concentration, stability, drug loading, and drug release characteristics. It was observed that the cross-linked micelles were stable upon excessive dilution compared to their non-cross-linked counterparts. Importantly, the amount of passive drug release in neutral pH was considerably lower for the cross-linked micellar systems. Furthermore, treatment of MDA-MB-231 breast cancer cells with nontargeted and targeted cross-linked micelles demonstrated higher internalization of the targeted construct. In corroboration, in vitro assa...Continue Reading

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Citations

Apr 3, 2020·Biomaterials Science·Burcu Sumer BoluRana Sanyal
Sep 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Søren Mejlsøe, Ashok Kakkar

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