Synthesis of 1, 2, 3-triazole linked 5 fluorouracil - carbon dots -folate conjugates for target specific anticancer activity and cell imaging applications

Abstract

This work provides a unique strategy to anchor the individual properties of fluorophores, pharmacophores and receptors in a single platform using a copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Notably, this approach counters the long-term dispute associated with the target-specific drug delivery of 5 fluorouracil and its intracellular tracing. Significantly, the luminescence property of the carbon dots (CDs) and the anticancer activity of the 5 fluorouracil drug are well preserved, even after their structural modification. The resulting nano-hybrid conjugate shows good thermal stability, photo-stability and can selectively guide the drug molecule toward cancer cells and remain nontoxic to noncancerous (hFB) cells. The conjugation of folic acid to the nanohybrid surface promoted the folate receptor-facilitated endocytosis to the folate-positive (HeLa) cell lines over the folate-negative (MCF-7) cells, which enhanced cellular uptake and corresponding better cell apoptosis results. Around 18.2% of cell apoptosis (late + early) values were recorded for the folate-conjugated formulation compared to the folate-less formulation (12.3%) and pure 5 FU drug (7.9%) by a flow cytometry study. Cell cycle analysis confirmed that the populations of HeLa cells in the S phase were around 18.20% and 29.8% for the folate-less formulation and the folate-conjugated formulation, indicating all the formulations can hinder the DNA replication and thymidylate synthesis by introducing cell cycle arrest in the S phase, just like the pure 5 FU drug. Also, the location of the drug molecule can be simultaneously traced because of the luminescent nature of the CDs. Therefore, the developed system has potential in target-specific drug delivery and long-term drug molecule tracking applications.