Multifunctional Envelope-Type Mesoporous Silica Nanoparticles\nfor Tumor-Triggered Targeting Drug Delivery

Abstract

A novel type of cellular-uptake-shielding\nmultifunctional envelope-type\nmesoporous silica nanoparticle (MEMSN) was designed for tumor-triggered\ntargeting drug delivery to cancerous cells. β-Cyclodextrin (β-CD)\nwas anchored on the surface of mesoporous silica nanoparticles via\ndisulfide linking for glutathione-induced intracellular drug release.\nThen a peptide sequence containing Arg-Gly-Asp (RGD) motif and matrix\nmetalloproteinase (MMP) substrate peptide Pro-Leu-Gly-Val-Arg (PLGVR)\nwas introduced onto the surface of the nanoparticles via host–guest\ninteraction. To protect the targeting ligand and prevent the nanoparticles\nfrom being uptaken by normal cells, the nanoparticles were further\ndecorated with poly­(aspartic acid) (PASP) to obtain MEMSN. <i>In vitro</i> study demonstrated that MEMSN was shielded against\nnormal cells. After reaching the tumor cells, the targeting property\ncould be switched on by removing the PASP protection layer via hydrolyzation\nof PLGVR at the MMP-rich tumor cells, which enabled the easy uptake\nof drug-loaded nanoparticles by tumor cells and subsequent glutathione-induced\ndrug release intracellularly.