Polyphosphate-Mediated Crystallographic and Colloidal Stabilization of CuS Nanoparticles: Enhanced NIR-Responsive Chemo-Photothermal Efficacy

Photothermal therapy (PTT) is an emerging treatment modality for cancer management. However, the photothermal agents (PTAs) used in PTT should have sufficient biocompatibility, water dispersibility, and good photoresponsive. In this aspect, water-dispersible and biocompatible linear polyphosphate (LP)-functionalized CuS nanoparticles (LP-CuS NPs) were developed using sodium tripolyphosphate (LP molecule) as a surface passivating agent. The successful formation of the green covellite CuS phase was confirmed by X-ray diffraction and TEM analyses, and its surface functionalization with the LP ligand was evident from X-ray photoelectron spectroscopy, Fourier transform infrared, thermogravimetric analysis, and light scattering measurements. It has been found that the use of LP not only stabilizes the crystallographic covellite CuS phase by overcoming the requirement of a soft ligand but also provides long-term aqueous colloidal stability, which is essential for PTT applications. The aqueous suspension of LP-CuS NPs showed excellent heating efficacy under near infrared (NIR) light irradiation (980 nm) and has a strong binding affinity towards anticancer drug, doxorubicin hydrochloride (DOX). The drug-loaded systems (DOX@LP-CuS NPs) revealed a pH-dependent drug release behavior with higher concentrations in a mild acidic environment. The in vitro studies showed substantial cellular uptake of DOX-loaded systems in cancer cell lines and enhanced toxicity towards them upon irradiation of NIR light through apoptotic induction, suggesting their potential application in chemo-photothermal therapy.