Multifunctional Mesoporous Silica Nanoparticles Based on Charge-Reversal Plug-Gate Nanovalves and Acid-Decomposable ZnO Quantum Dots for Intracellular Drug Delivery

A novel type of pH-responsive multifunctional mesoporous silica nanoparticle (MSN) was developed for cancerous cells drug delivery and synergistic therapy of tumor. MSNs were covered with a kind of cell-penetrating peptide, decalysine sequence (K-10), to enhance their escape from the endosomes. After K-10's primary amines were reacted with citraconic anhydride to form acid-labile beta-carboxylic amides, zinc oxide (ZnO) quantum dots (Q_Ds) were introduced to cap MSNs via electrostatic interaction. The obtained ZnO@MSN drug-delivery system (DDS) achieves zero-premature drug release under a physiological environment. However, once the DDS is transferred to the cancerous cells' acidic endosome, ZnO QDs would rapidly dissolve and the acid-labile amides on the side chain of K-10 would hydrolyze to regenerate primary amines, resulting in the uncapping of MSNs and exposure of the cell-penetrating peptide K-10. The regenerated K-10 could help the DDS escape from the endosome and efficiently release the loaded drugs inside the cells. At the meantime, because of the cytotoxicity of ZnO QDs at their destination, the ZnO@MSN DDS may achieve a synergistic antitumor effect to improve the therapeutic index.