Biocompatible pH-Responsive Luminescent Coacervate Nanodroplets from Carbon Dots and Poly(diallyldimethylammonium chloride) toward Theranostic Applications

Abstract

Photostable and inherently luminescent biocompatible nanomaterials have tremendous importance in biomedical research. Herein, we have designed a pH-responsive inherently luminescent carbon dot (CD)-based coacervate nanodroplet (ND) in the presence of cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC). The physicochemical and photoluminescence (PL) properties of these NDs have been explored as a function of equilibration time (1 and 18 h), pH (2-12), and ionic strength (1-1000 mM NaCl) by using various spectroscopic and microscopic techniques. Equilibrating the binary mixture of CD and PDADMAC for 1 and 18 h results in the formation of smaller (73.0 ± 2.3 nm) and larger sized (∼400 nm) NDs (SNDs and LNDs), respectively. While these NDs are stable in a broad pH range (5-12) and low ionic strength (<200 mM) medium, they disassembled in lower acidic pH (<5.5) and a high ionic strength (>200 mM) medium. Using UV-vis and confocal laser scanning microscopy, we have demonstrated that these negatively charged (ζ-potential = -17.0 ± 0.5 mV) NDs can spontaneously sequester neutral, cationic, and anionic dyes inside their porous nanostructure without any aggregation or structural disruption. In addition, a high partition coefficient of 10.6 ± 1.1 has been estimated for the cationic anticancer drug doxorubicin toward these NDs. The cell viability assay of SNDs with kidney fibroblast cell lines (BHK-21) reveals excellent biocompatibility. Finally, the bare and ethidium bromide (EtBr)-loaded SNDs have been utilized toward time-dependent cellular uptake experiments. Our findings indicate that the internalized SNDs undergo disassembly at lower acidic pH of late endosomes/lysosomes. While released EtBr in the cytosol specifically bind with nucleic acid within the cell nucleus without losing their affinity, free CDs on the other hand stain the whole cell without any specificity. Taken together, our present findings highlight the potential of these biocompatible inherently luminescent pH-responsive NDs toward theranostic applications. © 2020 American Chemical Society.