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

pH/enzyme-responsive nanocarriers based on porous silica (pSiO₂) nanospheres (NSs) were developed for controlled release of drug. The pSiO₂ NSs present uniform spheres and have an average diameter of 100nm. The pSiO₂ NSs with high specific surface area (835m²·g^-1) and the pore volume (1.24cm³·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 pSiO₂ NSs to conjugate the capping lids. Acid-decomposable ZnO quantum dots (QDs) were introduced to block the partial pores of pSiO₂ 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 pSiO₂, 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 pSiO₂ delivery system would achieve minimized premature release and responsive release under a physiological environment.