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 work, we designed and comparatively evaluated β- and γ-cyclodextrin-functionalized carbon dots (β-Cyd-CDs and γ-Cyd-CDs) as nanocarriers for the anthracycline drug doxorubicin (DOX), with the aim of elucidating how cyclodextrin cavity size influences drug–carrier interactions and release behavior. Spectroscopic analyses confirmed DOX binding through inclusion complex formation, leveraging the luminescent behavior of CDs to monitor interaction events. Drug loading studies revealed that β-Cyd-CD exhibited significantly higher loading efficiency than γ-Cyd-CD, highlighting the influence of cyclodextrin cavity size on host–guest complexation with doxorubicin. Drug release experiments under physiological-like conditions revealed a moderated and sustained release profile, with release rates approximately 25–60% slower than free DOX, attributed to the combined effects of cyclodextrin inclusion and surface interactions within the nanoplatform. In vitro assays demonstrated that DOX-loaded Cyd-CDs retained potent antiproliferative activity against tumor cells while exhibiting reduced cytotoxicity toward normal fibroblasts. These findings demonstrate that cyclodextrin-functionalized carbon dots constitute a versatile supramolecular nanoplatform for controlled drug delivery, where host–guest interactions can be rationally tuned to modulate drug loading and release behavior.