Acid-Liable Cleavage of Doxorubicin@Plunoric-Carbon Dots in Multiplexed Bioimaging and Drug Delivery.

This study reports the generation of novel, aqueous-dispersible plunoric-CD nanoconjugates encapsulating doxorubicin (Dox). The fluorescent CD were conjugated with plunoric F127 to form biocompatible delivery matrix and were further loaded with fluorescent Dox molecule. The resulting particles were analyzed for multiplexed bioimaging and targeted drug delivery. Physicochemical and optical characterization demonstrated discrete fluorescence from CD (blue emission) and Dox (orange emission) counterparts. In vitro drug release profile signifies higher and rapid release of Dox from Dox@Plu-CD under acidic conditions compared to physiological pH. Thus, the acid liable Dox@Plu-CD linkage can easily break in the cytosol of tumor cells because of low pH compared to normal cells thus conferring minimal damage to healthy cells. Moreover, results form in vitro cell viability assay suggest the cyto-compatibility of Plu-CD delivery matrix to HEK293 and HeLa cell lines. However, Dox@Plu-CD induced cell death and morphological alterations in HeLa cell lines, signifying pH-responsive effect of the prepared complex. Confocal imaging signified that Dox@Plu-CD effectively penetrates HeLa cells, and the released Dox binds to the cell nucleus and induces oxidative stress. The prepared Dox@Plu-CD thus behaved as efficient fluorescent probes allowing multiplexed bioimaging (blue and orange) of HeLa cells along with improved therapeutic potential.Graphical abstract.