Development of hyaluronate tethered magnetic nanoparticlesfor targeted anti-cancer drug delivery

Abstract

Despite the tremendous progress in understanding the molecular basis of the disease, cancer still remains one of the leading causes of deaths. Recently, advances in nanotechnology are rapidly enabling the development of novel, multifunctional materials with combined cancer specific targeting, therapeutic and diagnostic functions within a single nanocomplex (NP) that address the shortcomings of traditional disease diagnostic and therapeutic agents. Among the myriad of nanocarriers, magnetic nanoparticles (MNPs) have sparked extensive promise as novel theranostic applications as these MNPs can be directly targeted to the diseased cells with effective therapeutic efficiency. For this, these MNPs should be modified with some highly biocompatible polymers (specially polysaccharides) exhibiting the cancer targeting properties that can strongly interact with receptors expressed on the target cancer to facilitate accurate detection of the specific cancer and enhanced delivery to the target site while reducing unintended tside effects. Over the last few years, many groups have reported hyaluronic acid (HA) as the targeting agent as it directly delivers targeted MNPs to CD44 overexpressed cancer cells. In most of the cases, doxorubicin (DOX) has been used as the anticancer drug as it is largely utilized for treating a broad spectrum of cancers. In our work, we have designed a novel, intravenously injectable, CD44 receptor targeted MNP formulation, where the HA moiety of MNPs facilitate easy detection of cancer cells via receptor specific interactions, DOX can regress the cancer cells with simultaneous imaging efficacy. This theranostic MNPs led to the formation of novel nanoformulation, capable of performing concomitant detection, regression and imaging in in vitro CD44 over expressing cancer cells.