Construction of pH/reduction dual responsive MSN-HAgel containing HApt for tumor targeting carriers

Yehong Liu; Miaoxin Chen; Gaoyang Li; Shouhong Xu; Honglai Liu

doi:10.1039/d2ra02290g

Construction of pH/reduction dual responsive MSN-HAgel containing HApt for tumor targeting carriers

RSC Adv. 2022 Jun 29;12(30):19063-19071. doi: 10.1039/d2ra02290g.

Authors

Yehong Liu¹, Miaoxin Chen¹, Gaoyang Li¹, Shouhong Xu¹, Honglai Liu¹

Affiliation

¹ State Key Laboratory of Chemical Engineering and School of Chemistry & Molecular Engineering, East China University of Science and Technology Shanghai 200237 P.R. China xushouhong@ecust.edu.cn.

Abstract

In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HA₃₀₀₀gel and MSN-HA₁₁₀₀₀gel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of "1 + 1 > 2", providing a novel idea for cancer treatments.