A copper-free click reaction for the synthesis of redox-responsive water-soluble core cross-linked nanoparticles for drug delivery in cancer therapy

Abstract

Polymer based core cross-linked nanoparticles (CCNPs) have generated a lot of interest as potential stimuli-responsive drug delivery systems. In the present work, we have synthesized smart redox-responsive water soluble polymeric CCNPs by cross-linking water-soluble PEG based copolymers with bis(acryloyl)cystamine via isoxazoline bond formation through a 1,3-dipolar cycloaddition reaction (click reaction) without using a copper catalyst, in a water–THF mixed solvent. The successful synthesis of CCNPs was confirmed by NMR, GPC and FT-IR measurements. Size distribution of the precursor copolymers and the CCNPs was determined by DLS measurement. AFM and FESEM images have confirmed globular morphology of these CCNPs. Their high stability in a physiological environment makes them effective as potent drug carriers with high loading capacity. MTT assays confirmed the biocompatibility of the synthesized CCNPs. Favourable cellular internalization of these DOX loaded CCNPs into cancer cells and redox-responsive release of DOX therefrom make these CCNP potentially smart vehicles to deliver anticancer drugs into cancer cells.