Construction of multifunctional porous silica nanocarriers for pH/enzyme-responsive drug release

pH/enzyme-responsive nanocarriers based on porous silica (pSiO 2 ) nanospheres (NSs) were developed for controlled release of drug. The pSiO 2 NSs present uniform spheres and have an average diameter of 100   nm. The pSiO 2 NSs with high specific surface area (835   m 2 ·g −   1 ) and the pore volume (1.24   cm 3 ·g −   1 ) are suitable for drug loading and the loading capacity reaches to 29% for amoxicillin (AMX) model drug. In this system, protocatechuic acid (PCA) and L-glutamic acid (Glu) as linkers were grafting onto the surface of pSiO 2 NSs to conjugate the capping lids. Acid-decomposable ZnO quantum dots (QDs) were introduced to block the partial pores of pSiO 2 via amido bonds, which could act as gates and fluorescence probes. To minimize the premature release, hyaluronic acid (HA) was further coating on the outer surface of pSiO 2 , which would be degraded by over-expressed hyaluronidase (Hyal-1) in the tumor microenvironment. The controlled release of the drug from the ZnO/HA-gated delivery system was realized by the acidic dissolution of ZnO QDs and enzymatic hydrolysis of HA. The obtained ZnO/HA-gated pSiO 2 delivery system would achieve minimized premature release and responsive release under a physiological environment.