Redox‐Responsive Core Cross‐Linked Micelle as Anticancer Drug Delivery Vehicle

ABSTRACT Self‐assembled micelles are popular as a nanoplatform for cancer therapeutics. However, they still suffer from several drawbacks, like lower drug loading capacity and premature drug release. In order to overcome these issues, we have presently developed new redox‐responsive cross‐linked micelles using lipoic acid‐containing polymers, poly(NVP)‐ b ‐poly(LABPA). The self‐assembly behavior of the polymers was monitored before and after cross‐linking in the presence of a catalytic amount of glutathione (GSH). The core cross‐linked (CCL) polymeric micelles were further subjected to high GSH concentrations found in cancer cells, and the corresponding de‐cross‐linking of the core, followed by an analogous size change, was investigated using dynamic light scattering (DLS) and AFM measurements. In comparison to precursor polymers, the higher drug (doxorubicin; DOX) loading capacity (DLC) of 24.5% of the CCL micelles and GSH‐triggered rapid drug release suggested their importance as a potent drug delivery system for cancer therapy. Very often, a successful cancer treatment is inhibited by the drug resistance of the cancer cells. In this present work, the in vitro cytotoxicity study was performed using drug‐sensitive and drug‐resistant MDA‐MB‐231 cells, where a lower IC 50 value of the drug‐loaded CCL micelles was obtained in comparison to free DOX toward both drug‐sensitive and resistant cells, justifying their potential utility in cancer therapeutics. Briefly, our lipoic acid‐containing redox‐responsive polymers, poly(NVP)‐ b ‐poly(LABPA), show significantly enhanced drug loading capacity (24.5%), wonderful extracellular stability with rapid GSH‐triggered drug release in the intracellular redox environment, and importantly, the DOX‐loaded CCL micelles show significantly lower IC 50 values for both the parental and resistant cancer cells than free DOX, calling attention to their efficiency over other existing drug delivery vehicles.