Construction of pH and Redox Dual-ResponsiveMesoporous Silica Nanocarriers for Doxorubicin Deliveryin Ovarian Cancer TreatmentJun
Received: 18-03-2026
Revised: 20-04-2026
Accepted: 21-05-2026
Published in Issue 31-10-2026
Copyright (c) 2026 Jun Lou, Jun Zhu, Yin Bao, Jun Gao, Jiang Yan, Xiaorong Yang (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.
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Abstract
Mesoporous silica nanoparticles (MSNs) were engineered with a cystamine linker and a hyaluronic acid (HA) shell to create a pH- and redox-responsive carrier for doxorubicin (DOX) delivery to SKOV3 ovarian cancer cells. Transmission electron microscopy showed spherical cores with an average diameter of about 95 nm. Nitrogen sorption analysis gave a BET surface area of 1025.4 ± 15.2 m²/g, a total pore volume of 1.12 ± 0.03 cm³/g, and a mean pore diameter of 2.75 ± 0.05 nm for the bare MSNs. Surface functionalization increased the hydrodynamic diameter from 115 nm to about 165 nm and shifted the zeta potential from -28.5 mV to +32.4 mV after amination and to -35.1 mV after HA conjugation. The final formulation achieved 22.5 wt% loading with encapsulation efficiency above 85%. Drug release remained limited at pH 7.4 without glutathione (12% at 72 h), increased under acidic conditions (about 38% at pH 5.0), and reached about 88% under combined acidic and reducing conditions. Free HA reduced uptake by about 65%, supporting CD44-mediated internalization. Blank carriers maintained >90% SKOV3 viability up to 500 μg/mL, whereas DOX@MSN-SS-HA produced greater time-dependent cytotoxicity than free DOX at 48-72 h and increased apoptosis to 68.7% at 48 h. Confocal imaging showed progressive intracellular accumulation with nuclear localization by 12 h. Together, these data support the use of HA-gated, disulfide-linked MSNs as a promising in vitro platform for stimulus-responsive DOX delivery, while further studies are needed to define normal-cell safety, hemocompatibility, pharmacokinetics, and in vivo efficacy.
Keywords
- CD44 targeting,
- Hyaluronic acid,
- Mesoporous silica nanoparticles,
- Ovarian cancer,
- Redox-responsive release
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10.57647/jnsc.2026.1605.24
