Gelatin–mesoporous silica nanoparticles as matrix metalloproteinases-degradable drug delivery systems in vivo

Abstract

The matrix metalloproteinases (MMPs) are a family of proteases which are normally up-regulated in tumor tissues. Gelatin is a biocompatible and non-immunogenic substrate which can be degraded by MMPs. In this work, MMPs-degradable gelatin coated mesoporous silica nanoparticles (MSNs@Gel) were designed for endogenous tumor microenvironment-triggered release systems for cancer treatment in vivo. This drug delivery system is expected to attain preferential release of drugs in tumor microenvironment with diminished systemic toxicity. The gelatin corona can serve as both a protective layer for preventing drugs leakage and MMPs-digested substrates for responding the solid tumor microenvironment. Doxorubicin (DOX), as a model antitumor drug, was loaded into the mesopores of MSNs@Gel to give DOX⊂MSNs@Gel with controllable releasing feature upon the MMPs stimuli. Interestingly, the encapsulated DOX in the DOX⊂MSNs@Gel was barely delivered into the normal cells due to the less endocytosis activity compared to that of the cancerous cells, resulting in the decreased systemic toxicity and decreased side effect during the tumor treatment. Whilst in the tumor tissue, the gelatin layer of DOX⊂MSNs@Gel was degraded and the encapsulated DOX was released effectively. The released DOX was accumulated in the nucleus of tumor cells. In vivo studies demonstrated that the tumor growth of xenografted mice was significantly delayed without any appreciable body weight loss that indicated the lower systemic toxicity of DOX⊂MSNs@Gel compared to the free DOX.