Gate Control of Mesoporous Silica Nanoparticle with a-Synuclein Coated Gold Nanoparticles and Its Application to Control of Cancer Metastasis

Abstract

Over the last few decades, various kinds of drug delivery systems including liposome, nano-capsule, synthetic polymer, and etc have continuously been developed to maximize the therapeutic effect of drugs. However, developing the novel gate-keeping system with a controllable release mechanism for preventing the pre-mature release of cargo is the challenge remained. Herein, we report construction of protease responsive drug delivery system with secured gate keeping effect and propose its application in the control of cancer metastasis. The drug delivery system is mesoporous silica nanoparticle based with its pores tightly capped by α-synuclein protein coated gold nanoparticles via the proteins unique adhesion property on silica surfaces. We have named it as the Particles on a Particle (PoP) system on account of its morphology that smaller particles are covering around a larger particle. In the in vitro cargo release test, using rhodamine6G dye as the model cargo, the PoP showed aorund 80% more effective gate keeping than bare system and the caps were stable at various pH ranges. Furthermore, selective cargo release was achieved by the digestion of α-synuclein by proteases such as trypsin, protease K and chymotrypsin. Protease inhibitor loaded PoP demonstrated its effectiveness in inhibiting the triggering protease indicating its usage in the treatment of the diseases where the level of certain protease is enhanced. As an expansion of this concept, the gate opening of PoP in the presence of matrix metalloproteinase, an endopeptidase known to facilitate the metastasis process of malignant tumor, was tested. Consequently, it was observed that PoP is responsive to matrix metalloproteinase and induced significant cargo release. These results emphasizes the potential of PoP as an enzyme responsive therapeutic nano-carrier which can prevent leaking of cargo and release drugs in response to the changes of patho-physicochemical microenvironment around the target disease.