Hyaluronic acid/PEGylated amphiphilic nanoparticles for pursuit of selective intracellular doxorubicin release

Abstract

Polyethylene glycol (PEG)-lyted cationic amphiphilic copolymers were employed as complexing agents with biocompatible anionic hyaluronic acid (HA) for the controlled release of doxorubicin (DOX). The overexpressed receptors to HA in a variety of cancerous cells enable preferential endocytosis of the HA-functionalized nanoparticles. Moreover, introduction of HA is supposed to diminish the unfavorable non-specific reactions in the biological milieu. Particularly, the drastic positive charge was validated post-endocytosis as a consequence of our strategic molecular design for the promotion of positive charges of cationic components. This deshielding effect of the anionic hyaluronic acid by endogenous hyaluronidase in endosomes and demotion of PEG at the endosome acid microenvironment consequently results in the structural rearrangement and favorable reaction of the resulting positive-charged structure with the intracellular species and structures, ultimately giving rise to liberation of the doxorubicin for the subsequent molecular pharmaceutic consequences. Simultaneously, the system containing quaternary ammonium salt and hydrophobic n-octyl acrylate (OA) possesses considerable antibacterial ability to alleviate anti-cancer drugs resistance. This delivery system is intended to overcome the intratumor bacteria-induced tumor resistance.