This research demonstrates a novel sealing method using stimuli-responsive polymers for drug delivery via porous silicon nanoparticles, suggesting enhanced stability and loading capacity.
Porous silicon nanoparticles (pSiNPs) represent a unique drug delivery candidate owing to the biocompatibility, degradability, high loading capacity as well as production scalability. Various endeavours have been reported to make practical formulations with pSiNPs. However, existing protocols still lack simplicity and sometimes stability in physiological environment. Herein, we report the use of stimuli-responsive poly(disulfide) as a sealing/coating strategy for pSiNPs. The polymer matrix was formed in one-pot protocols in water and various payloads, including small molecule drugs, drug conjugate and small interfering RNA (siRNA), could be loaded spontaneously. The engineered hybrid nanoparticles demonstrated excellent stability in saline and tuneable degradability. Drugs like doxorubicin (DOX) and camptothecin (CPT) were loaded physically by polymer entrapment, while disulfide-based self-immolative linker (SIL) were also used to covalently load CPT. To load macromolecular payload siRNA, we developed a polymerisable ionisable lipid (PIL) strategy to suit this sealing strategy. siRNA was loaded via electrostatic interactions followed by polymer entrapment. In vitro experiments revealed the successful delivery of therapeutic candidates in cells. These combined efforts provide a practical solution for the use of pSiNPs in drug delivery.
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Zhang et al. (2025) studied this question.
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