Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application

• Published in: ACS applied bio materials 2024-08, Vol.7 (8), p.5483-5495
• Main Authors: Kumawat, Akshant, Saini, Bhawna, Ghoroi, Chinmay
• Format: Article
• Language: English
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.4c00633

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.