Supramolecular nanoparticle carriers self-assembled from cyclodextrin- and adamantane-functionalized polyacrylates for tumor-targeted drug delivery

Abstract

The advancement of nanobiotechnology has led to the development of various techniques for addressing target-specific drug delivery issues. In this article, we successfully developed a supramolecular self-assembly approach for the fabrication of polyacrylate-based nanoparticles with simultaneous loading of the anticancer drug doxorubicin (DOX) for targeted delivery towards cancer treatment in vitro and in vivo. Two types of polyacrylates functionalized with adamantane and β-cyclodextrin respectively could self-assemble to form supramolecular nanoparticles through strong host–guest complexation between adamantane and β-cyclodextrin. Folic acid was incorporated within the supramolecular nanoparticles in order to impart the targeting specificity towards selected cancerous cell lines, namely MDA-MB231 and B16-F10. The as-synthesized supramolecular nanoparticles were fully characterized by several techniques, revealing an average nanoparticle size of 35 nm in diameter, which is small enough for excellent blood circulation. The cytotoxicity studies indicate that the supramolecular nanoparticles without drug loading were non-cytotoxic under the concentrations measured, while DOX-loaded supramolecular nanoparticles showed significant cytotoxicity. In order to investigate the targeting specificity of DOX-loaded supramolecular nanoparticles towards the cancerous cells, a healthy cell line model HEK293 was employed for carrying out the comparison studies. Due to the presence of the targeting ligand, experimental results demonstrate that the supramolecular nanoparticles were highly specific for targeting the cancerous cells, but not for HEK293 cells. After the in vitro investigations, the in vivo drug delivery study using DOX-loaded supramolecular nanoparticles was performed. Tumor-bearing nude mice were treated with DOX-loaded supramolecular nanoparticles, and the analysis results indicate that DOX-loaded supramolecular nanoparticles have the capability to enhance the therapeutic effects of DOX for effectively inhibiting the tumor growth. Thus, the self-assembled polymeric nanoparticles exhibit a highly promising potential to serve as drug carriers for targeted drug delivery towards improved cancer treatment.