Sealing Porous Silicon Nanoparticles with Stimuli‐Responsive Disulfide Polymers for Cellular Delivery

Porous silicon nanoparticles (pSiNPs) represent a unique drug delivery candidate owing to the biocompatibility, degradability, high loading capacity, and production scalability. Various endeavors have been reported to make practical formulations with pSiNPs. However, existing protocols still lack simplicity and sometimes stability in physiological environment. Herein, the use of stimuli‐responsive poly(disulfide)s as a sealing/coating strategy for pSiNPs is reported. The polymer matrix is formed in one‐pot protocols in water, and various payloads, including small molecule drugs, drug conjugate, and small interfering RNA (siRNA), are loaded spontaneously. The engineered hybrid nanoparticles demonstrated excellent stability in saline and tunable degradability. Drugs like doxorubicin (DOX) and camptothecin (CPT) are loaded physically by polymer entrapment, with loading efficiencies (LE) of 25% and 97%, and payload‐silicon ratios (P/Si) of 54% and 97%, respectively. A disulfide‐based self‐immolative linker (SIL) is also used to covalently load CPT (LE 93%, P/Si 12%). To load siRNA, a polymerizable ionizable lipid (PIL) strategy is developed. siRNA is loaded via electrostatic interactions followed by polymer entrapment (LE 36%, P/Si 14.4%). In vitro experiments reveal the successful delivery of therapeutic candidates in cells. These combined efforts provide a practical solution for the use of pSiNPs in drug delivery.