Novel Chitosan Derivatives with Reversible Cationization and Hydrophobicization for Tumor Cytoplasm-Specific Burst Co-delivery of siRNA and Chemotherapeutics

ACS Applied Materials & Interfaces
Tingjie YinMeirong Huo

Abstract

Despite the great potential of combination therapy based on siRNA and chemotherapeutics, an efficient vehicle with abilities of well drug co-loading, synchronizing in vivo trafficking, and target-specific co-burst release remains elusive, which results in a suboptimal synergistic potency. Herein, a novel chitosan amphiphile (PEI-ss-HECS-ss-OA, HSPO) with glutathione (GSH)-reversible cationization and hydrophobicization by polyethylenimine (PEI) and octylamine (OA), respectively, was developed for this purpose. HSPO spontaneously assembled in aqueous solution to be a micellar system and effectively co-encapsulated the two drugs with an adjustable dosage ratio. With a surface charge inversion strategy by hyaluronic acid (HA) coating, the HA(HSPO) co-delivery micelles with a negative surface charge (-21.45 ± 1.44 mV) and suitable size (192.52 ± 7.41 nm) selectively accumulated into CD44 overexpressed A549 tumors through a combination of passive and active targeting mechanism. Then, tumor cytoplasm-selective co-burst release was obtained through GSH triggered collapse of the amphiphilic assembly alongside a decrease of positive charge condensation, finally leading to an enhanced synergistic antitumor effect with a superior inhibiti...Continue Reading

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Citations

Aug 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jian SunZhaowei Chen
Sep 3, 2021·ACS Omega·Nechikkottil Sivadasan SumithaGopalakrishnanchettiar Sivakamiammal Sailaja
Oct 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Raut BholakantJan Feijen

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