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

TLDR

The study designs a cellular‑uptake‑shielding MEMSN for tumor‑triggered targeted drug delivery to cancer cells. MEMSNs feature β‑cyclodextrin linked by disulfide bonds for glutathione‑triggered release, surface RGD and MMP‑cleavable PLGVR peptides for targeting, and a poly(aspartic acid) shield that is removed by tumor‑rich MMPs to expose the ligands and trigger drug release. In vitro, MEMSNs were protected from normal cells and, upon MMP‑mediated removal of the shield, selectively entered tumor cells and released drugs via glutathione‑triggered mechanisms.

Abstract

A novel type of cellular-uptake-shielding multifunctional envelope-type mesoporous silica nanoparticle (MEMSN) was designed for tumor-triggered targeting drug delivery to cancerous cells. β-Cyclodextrin (β-CD) was anchored on the surface of mesoporous silica nanoparticles via disulfide linking for glutathione-induced intracellular drug release. Then a peptide sequence containing Arg-Gly-Asp (RGD) motif and matrix metalloproteinase (MMP) substrate peptide Pro-Leu-Gly-Val-Arg (PLGVR) was introduced onto the surface of the nanoparticles via host–guest interaction. To protect the targeting ligand and prevent the nanoparticles from being uptaken by normal cells, the nanoparticles were further decorated with poly(aspartic acid) (PASP) to obtain MEMSN. In vitro study demonstrated that MEMSN was shielded against normal cells. After reaching the tumor cells, the targeting property could be switched on by removing the PASP protection layer via hydrolyzation of PLGVR at the MMP-rich tumor cells, which enabled the easy uptake of drug-loaded nanoparticles by tumor cells and subsequent glutathione-induced drug release intracellularly.