Dual-Targeted, Ph/Reduction-Responsive Mesoporous Silica Nanocarriers for Selective Sorafenib Delivery to Hepatocellular Carcinoma Publisher



Perseh S ; Bafkary R ; Salmani H ; Shahriari M H ; Dinarvand R ; Haririan I ; Mojtabazadeh S S ; Jamshidfar S ; Akrami M
Source: Advanced Therapeutics Published:2026

Abstract

Targeted nanocarriers offer a promising platform to improve cancer therapy by increasing efficacy while reducing off-target toxicity. A novel multilayer, reduction- and pH-responsive nanocarrier was engineered by sequentially functionalizing mesoporous silica nanoparticles with hyaluronic acid and polyamidoamine dendrimers, followed by conjugation with carboxyphenylboronic acid for dual receptor-mediated targeting of hepatocellular carcinoma cells. The nanoparticles were characterized by dynamic light scattering, showing size growth from 242.1 nm (bare) to 344.4 nm after complete coating, and a zeta potential shift from −30.1 to −7.46 mV. BET analysis confirmed preserved mesopores, with specific surface area decreasing only 1.5% from 183.2 to 180.1 m2 g−1, maintaining high porosity for drug loading. Sorafenib loading reached an encapsulation efficiency of 32% and a loading capacity of 60.4%. In vitro release demonstrated stimulus responsiveness: 55.2% release at acidic pH 5.5 and 73.4% in the presence of 10 mM glutathione, vs. 20.2% at pH 7.4 without glutathione. In HepG2 cells, the targeted system yielded an IC50 of 7.6 µg/mL after 48 h, representing 1.8- and 1.25-fold improvements over sorafenib and non-targeted nanoparticles, respectively. The platform integrates HA-CD44 and carboxyphenylboronic acid with pH/redox-sensitive release for hepatocellular carcinoma therapy, offering to improve efficacy while reducing toxicity. © 2026 Wiley-VCH GmbH.