Multifunctional nanocarriers based on graphitic-C3N4 quantum dots for tumor-targeted, traceable and pH-responsive drug delivery

Abstract

Considering the intrinsic complexity of cancer, the emergence of multifunctional nanocarriers provides more possibilities for cancer therapy. Herein, a novel multifunctional nanocarrier (g-CNQDs–PEG–RGD) is successfully developed by covalently grafting graphitic-C₃N₄ quantum dots (g-CNQDs) with arginine–glycine–aspartic acid (RGD) via diamine-terminated oligomeric polyethylene glycol (PEG). The functionalization of g-CNQDs with PEG and RGD imparts the nanocomposite with low cytotoxicity, excellent physiological stability and specific targeting ability toward cancer cells with the α_vβ₃ receptor. The widely used fluorescent antineoplastic anthracycline drug doxorubicin (DOX) is non-covalently loaded onto g-CNQDs–PEG–RGD. It is advantageous that the g-CNQDs–PEG–RGD–DOX nano-assembly exhibits enhanced cellular uptake by HepG2 cells, which overexpress integrin α_vβ₃ receptors. Thus, the enhanced targeting specificity and intracellular acid condition-triggered drug release promise excellent therapeutic effects. Meanwhile, the inherent stable fluorescence of g-CNQDs–PEG–RGD and DOX enables real-time monitoring of cellular uptake of the g-CNQDs–PEG–RGD–DOX nano-assembly, consequent release of DOX and the fate of the carrier. These findings demonstrate that g-CNQDs–PEG–RGD–DOX will be promising for high treatment efficacy with minimal side effects in future therapy.