Engineering Functionalized Carbon Dots as Biocompatible Nanocarriers for Controlled Doxorubicin Delivery in Cancer Therapy

Abstract

Cancer remains one of the leading causes of mortality worldwide, emphasizing the urgent need for therapeutic strategies that are both effective and biocompatible. Advances in nanotechnology have enabled the development of innovative drug delivery systems with improved pharmacological profiles. Among these, Carbon Dots (CDs) have emerged as versatile nanomaterials owing to their intrinsic luminescence, facile synthesis, excellent biocompatibility, and antioxidant activity. Their surface modification with cyclodextrins (Cyds) further enhances functionality by enabling host-guest complexation with therapeutic molecules.In this study, we designed and characterized β-and γ-cyclodextrin-functionalized Carbon Dots (β-Cyd-CDs and γ-Cyd-CDs) as nanocarriers for the anthracycline drug doxorubicin (DOX). Spectroscopic analyses confirmed DOX binding through inclusion complex formation, leveraging the luminescent behavior of CDs to monitor interaction events. Drug release experiments under physiological-like conditions revealed a controlled and sustained release profile, exhibiting a 25-60% slower release compared with free DOX, attributed to efficient host-guest interactions. In vitro assays demonstrated that DOX-loaded Cyd-CDs retained potent antiproliferative activity against tumor cells while exhibiting reduced cytotoxicity toward normal fibroblasts.These results support the potential of cyclodextrin-functionalized Carbon Dots as biocompatible nanocarriers for targeted and controlled delivery of anticancer agents. This approach may contribute to the development of safer and more effective nanotechnology-enabled chemotherapeutic formulations.