Tumor targeted delivery of umbelliferone via a smart mesoporous silica nanoparticles controlled-release drug delivery system for increased anticancer efficiency.

Abstract

Herein, a mesoporous silica nanoparticle (MSN) based biocompatible, targeted and controlled drug delivery system has been synthesized for tumor tissue-specific drug delivery. Umbelliferone, a natural coumarin derivative was loaded into the pores of MSN and capped with pH-sensitive poly acrylic acid (PAA). For targeted delivery of umbelliferone in tumor tissue, folic acid (FA) was grafted onto the surface of drug-loaded and PAA-coated MSN. The successful construction of the nanohybrid (Umbe@MSN-PAA-FA) was confirmed by performing a series of characterization. The synthesized pH-responsive nanohybrid showed diameter of around 50nm with overall negative surface charge and drug loading content of 12.56%. In vitro study showed that the nanohybrid caused significant cytotoxicity through the induction of both oxidative stress as well as mitochondrial damage in folate receptor over-expressed in human breast cancer cell, MCF-7 compared with free umbelliferone. In vivo study also exhibited that the nanohybrid effectively reduced tumor growth in tumor-bearing mice compared with free umbelliferone due to the enlarged bioavailability of the drug in tumor tissue. Besides, the nanohybrid did not exhibit any significant sign of systemic toxicity in other vital organs. Together, the study denoted that PAA and FA functionalized MSN controlled-drug delivery system could assist to increase the anticancer potential of umbelliferone.