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We designed, for the first time, an enzyme-triggered drug and gene codelivery system combining hollow mesoporous silica (HMS) with enzyme degradable poly(l-lysine) (PLL) polymer to form HMS/PLL particles driven by electrostatic interaction between negatively charged gene and positively charged PLL polymer on the drug-loaded HMS particles. Fluorescein and cytosine–phosphodiester–guanine oligodeoxynucleotide (CpG ODN) were used as the model drug and gene, and the loading and the layer-by-layer assembly were evaluated by UV/vis analysis, zeta potential measurement, and gel electrophoresis. The fluorescein and CpG ODN loading capacities of the MFHMS/(CpG/PLL)3 particles were 28.8 and 97.1 μg/mg, respectively. Importantly, in vitro release results showed that the MFHMS/(CpG/PLL)3 particles exhibited an enzyme-triggered controlled release of fluorescein and CpG ODN simultaneously in the α-chymotrypsin solution, and the release rates of fluorescein and CpG ODN could also be controlled by changing the enzyme concentration. Therefore, this system has the advantages of both enzyme-triggered controlled release and codelivery of drug and gene and would have potential and promising applications in the field of biomedicine and cancer therapy

Hollow Mesoporous Silica/Poly(l-lysine) Particles for Codelivery of Drug and Gene with Enzyme-Triggered Release Property