Multi-responsive upconversion/organic porous silicon nanocomposite for controlled drug release via NIR irradiation and tumor microenvironment stimuli

We report the synthesis of an organic/inorganic architecture, a rare-earth upconversion nanoparticle (UCNP)-based core with organic porous silicon shell nanocapsules, that enables visible and ultraviolet light emission under 980 nm near-infrared (NIR) irradiation for photodegradation. A mesoporous organosilica shell containing disulfide bonds was uniformly coated onto UCNP cores via a combined sol–gel and hard-template strategy. Glutathione (GSH) – triggered degradation of the nanocarriers was quantified using the molybdenum blue method. A photoresponsive azobenzene derivative, activatable by both UV and visible light, was synthesized and grafted onto the nanocarrier surface. Doxorubicin (DOX) was loaded into the nanocapsules, achieving a drug-loading capacity of 12.2 wt%. At neutral pH, minimal DOX leakage occurred; maximal release was observed under a composite stimulus environment. The Baker-Lonsdale model was employed to calculate diffusion coefficients under varying release conditions, providing quantitative guidance for designing multi-responsive drug-release systems. In vitro cellular assays showed that synergistic stimuli—NIR irradiation combined with an acidic, GSH-rich microenvironment—trigger controllable DOX release, enabling efficient tumor cell ablation. This work demonstrates a versatile, multi-responsive delivery platform combining UCNP-based photoreactivity, GSH-triggered degradation, and photoactive surface gating to achieve targeted, low-toxicity, on-demand chemotherapy.