Chitosan-mediated green synthesis and folic-acid modification of CuS quantum dots for photoacoustic imaging guided photothermal therapy of tumor

Abstract CuS nanomaterials capped with artificial organic-molecules or polymers have been well demonstrated as efficient photothermal nanoagents for the therapy of tumor, but their biocompatibility and target ability should be improved. To address these problems, we have used chitosan (CS) as the biomacromolecule model and surface ligands to prepare CuS quantum dots (QDs) via a simple co-precipitation method. CuS-CS QDs are then conjugated with folic acid (FA). The resulting CuS-CS-FA QDs are composed of hexagonal phase nanodots with sizes of about 4 nm. FA modification process has no apparent influence on the size, phase and composition of the QDs. Furthermore, the zeta potential and infrared spectroscopy confirm the efficient conjugation of FA. CuS-CS-FA QDs exhibit strong near-infrared photoabsorption and high photothermal efficiency (47.0%). As a result of the presence of CS ligand and FA modification, CuS-CS-FA QDs have good biocompatibility and relatively high cellular uptake efficacy. When CuS-CS-FA QD dispersion is injected intravenously into the tumor-bearing mice, the photoacoustic imaging reveals that CuS-CS-FA QD can be efficiently targeted and accumulated in the tumor and reach the peak dose at 60 min. The irradiation of 1064-nm laser (1.0 W cm-2, 10 min) results in the efficient inhibition of tumor growth, without treatment-induced toxicity. Therefore, CuS-CS-FA QDs have great potential to become biocompatible multifunctional nanoagents for imaging guided therapy of tumor.