Bridged polysilsesquioxanes (BPSs) are emerging biomaterials composed of synergistic inorganic and organic components. These materials have been investigated as ideal carriers for therapeutic and diagnostic systems for their favorable properties, including excellent biocompatibility, physiological inertia, tunable size and morphology, and their extensive design flexibility of functional organic groups to satisfy diverse application requirements. Stimuli-responsive BPSs can be activated by both endogenous and exogenous stimuli, offering a precise, safe, and effective platform for the controlled release of various targeted therapeutics. This review aims to provide a comprehensive overview of stimuli-responsive BPSs, focusing on their synthetic strategies, biocompatibility, and biodegradability, while critically assessing their capabilities for controlled release in response to specific stimuli. Furthermore, practical suggestions and future perspectives for the design and development of BPSs are presented. This review highlights the significant role of stimuli-responsive BPSs in advancing biomedical research.

Developing stimuli-responsive nanoplatforms is a promising strategy for controlling the release of targeted molecules. In this study, nitrobenzyl ester was chosen as a photoresponsive moiety to functionalize an organic bridged linker, facilitating the synthesis of a photoresponsive silane, namely 2-nitro-1,3-phenyl bis(methylene mercaptoacetate ester) bridged trimethoxysilane (SMS). Light-triggered degradable bridged polysilsesquioxane nanoparticles (SMPS) were achieved through hydrolysis-condensation reactions using SMS as a precursor in suspension polymerization. Upon irradiation at 365 nm for three hours, the particle size of SMPS decreased from 138 ± 20 nm to 103 ± 43 nm. The target molecule, evodiamine (Evo), was efficiently loaded onto SMPS through hydrophobic and electrostatic attractions, constructing a light-controlled release system, Evo@SMPS. The results of in vitro experiments demonstrate that this photoresponsive platform exhibits effective light-triggered release behavior upon 365 nm. Under an irradiation intensity of 100 mW cm⁻² for 12 hours, the cumulative release rate of Evo reached up to 92.3%, allowing precise control over the release amount, timing, and location of target molecules. This light-triggered degradable bridged polysilsesquioxane carrier platform with high biocompatibility holds significant potential and prospects for broad application in multifunctional controlled release systems.