Targeted Delivery of Doxorubicin via CD147-Mediated ROS/pH Dual-Sensitive Nanomicelles for the Efficient Therapy of Hepatocellular Carcinoma

The AAPS Journal
Chen-Xi QuXue-Nong Zhang

Abstract

Low accumulation in tumor sites and slow intracellular drug release remain as the obstacles for nanoparticles to achieve effective delivery of chemotherapeutic drugs. In this study, multifunctional micelles were designed to deliver doxorubicin (Dox) to tumor sites to provide more efficient therapy against hepatic carcinoma. The micelles were based on pH-responsive carboxymethyl chitosan (CMCh) modified with a reactive oxygen species (ROS)-responsive segment phenylboronic acid pinacol ester (BAPE) and an active targeted ligand CD147 monoclonal antibody. The Dox-loaded micelles provided rapid and complete drug release in pH 5.3 incubation conditions with 1 mM H2O2. In addition, an in vitro cell uptake study revealed that CD147 modification significantly enhanced cellular internalization due to the high affinity to CD147 receptors, which are overexpressed on tumor cells. An in vivo study revealed that CD147-modified micellar formulations exhibited high accumulation in tumor sites and markedly enhanced antiproliferation effects with fewer side effects than other formulations. In conclusion, this CD147 receptor targeted delivery system with ROS/pH dual sensitivity provides a promising strategy for the treatment of hepatic carcinoma.

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Methods Mentioned

BETA
amidation
Protein Assay
Nuclear Magnetic
Dynamic light scattering
flow cytometry

Software Mentioned

SPSS

Related Concepts

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