Dual CEA/CD44 targeting to colorectal cancer cells using nanobody-conjugated hyaluronic acid-modified mesoporous silica nanoparticles with pH- and redox-sensitivity

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death among all malignancies. Drug delivery targeting tumor surface receptors improve therapeutic effects and lower side-effects since they can increase the drug accumulation in target tissues and cellular uptake. In this study, we established a pH- and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) for the delivery of the anticancer drug doxorubicin hydrochloride (DOX). In this drug delivery system, MSNs-NH2 were modified with hyaluronic acid (HA) to form a highly loaded anticancer drug core; they were further coated with 11C12, a nanobody against carcinoembryonic antigen (CEA) to form a guiding outer layer (DOX@MSNs-HA-11C12). The accurate localization of nanoparticles would be mediated by two targeting molecules HA and nanobody 11C12, which target the CD44 receptor and the proximal membrane end of CEA on the surface of CRC cells, respectively. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, and (pH 7.4 + GSH) < (pH 6.8 + GSH)