Fabrication of Folic Acid-Derived Carbon Dot-Conjugated Chitosan Nanospheres as Theragnostic Agents for pH-Responsive Anticancer Drug Delivery

Abstract

The favorable success rate in cancer treatment predominantly depends on precise diagnosis with target-specific drug delivery, which can regulate the patient survival outcome rate. Moreover, proper tracking of the system's pH is very much crucial as most of the therapeutic's action and release rate depend on it. Therefore, this work has been intended to fabricate a folic acid-derived carbon dot (FACD) decorated with chitosan (Cs) in order to form nanospheres (FACD-Cs-Ns) for anticancer doxorubicin hydrochloride (Dox.HCl) drug delivery through imaging in cancer therapeutic treatment. The engineered FACD-Cs-Ns demonstrated a spherical shape with an extensive surface area, rich in carboxyl and hydroxyl groups that play a key role in its pH-responsive characteristics through protonation and deprotonation interactions. Thanks to their impressive fluorescence traits and excellent stability, FACD-Cs-Ns are particularly well suited for imaging-guided cancer therapy. Their remarkable cytocompatibility with normal cells and significant toxicity toward cancer cells, along with pH-responsive properties, render them as ideal candidates for targeted drug delivery to cancer cells. The G2/M and S phases' arrest in the cell cycle analysis study once more validated excellent <i>in vitro</i> experimental conditions. The impressive selectivity and cytotoxicity of Dox-loaded FACD-Cs-Ns toward cancer cells can be attributed to enhanced cellular uptake via folate-receptor-mediated endocytosis, which is overexpressed in these cells. These findings elucidate that the FACD-Cs-Ns nanoprobe is an excellent material for pH-responsive anticancer drug delivery and image-guided cancer therapy.