Hyaluronic Acid–targeted Polyethyleneimine Nanodrug Carrier: Construction And Tumor Therapy Applications

Chemical drug treatment is one of the most important cancer treatments. Common anti-tumor drugs have some problems, such as poor water-solubilioty, side effects, fast metabolism. And it cannot target to the tumor site, which results in normal tissue and organ damage. The objective of our study is to reduce material toxicity, to improve the biocompatibility, and to make drug have tumor targeting specificity.It is generally required to develop a nanocarrier system that is able to improve the water solubility of the anticancer drug and enables targeted delivery of the drug to cancer cells via receptor-mediated endocytosis pathway. In this work, polyethyleneimine(PEI) was sequentially modified with dual functional polyethylene glycol(NH2-PEG-COOH), hyaluronic acid(HA), and fluorescein isothiocyanate(FI). The prepared PEI-FI-(PEG-HA) conjugate was then used as a nanoplatform to encapsulate anticancer drug doxorubicin(DOX). We show that the formed PEI-FI-(PEG-HA) conjugate is able to encapsulate approximately 19 DOX molecules within each multifunctional PEI, and the formed PEI-FI-(PEG-HA)/DOX complexes can release DOX in a pH-dependent manner with a higher DOX release rate under an acidic pH condition than under a physiological pH condition. In addition, the PEI-FI-(PEG-HA)/DOX complexes are able to specifically target cancer cells overexpressing CD44 receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and thus deliver DOX to the target cancer cells to inhibit their growth. The developed HA-targeted PEI may hold great promise to be used as an efficient nanoplatform for targeted delivery of different anticancer drugs.