*Article* **Transforming Commercial Copper Sulfide into Injectable Hydrogels for Local Photothermal Therapy**

**Xiaoran Wang 1,†, Zizhen Yang 1,†, Zhaowei Meng 1,\* and Shao-Kai Sun 2,\***


**\*** Correspondence: zmeng@tmu.edu.cn (Z.M.); shaokaisun@tmu.edu.cn (S.-K.S.); Tel.: +86-186-2203-5159 (Z.M.);

† These authors contribute equally to the work.

**Abstract:** Photothermal therapy (PTT) is a promising local therapy playing an increasingly important role in tumor treatment. To maximize PTT efficacy, various near-infrared photoabsorbers have been developed. Among them, metal sulfides have attracted considerable interest due to the advantages of good stability and high photothermal conversion efficiency. However, the existing synthesis methods of metal-sulfide-based photoabsorbers suffer from the drawbacks of complicated procedures, low raw material utilization, and poor universality. Herein, we proposed a flexible, adjustable strategy capable of transforming commercial metal sulfides into injectable hydrogels for local PTT. We took copper sulfide (CuS) as a typical example, which has intense second-window near-infrared absorption (1064 nm), to systematically investigate its in vitro and in vivo characteristics. CuS hydrogel with good syringeability was synthesized by simply dispersing commercial CuS powders as photoabsorbers in alginate-Ca2+ hydrogel. This synthesis strategy exhibits the unique merits of an ultra-simple synthesizing process, 100% loading efficiency, good biocompatibility, low cost, outstanding photothermal capacity, and good universality. The in vitro experiments indicated that the hydrogel exhibits favorable photothermal heating ability, and it obviously destroyed tumor cells under 1064 nm laser irradiation. After intratumoral administration in vivo, large-sized CuS particles in the hydrogel highly efficiently accumulated in tumor tissues, and robust local PTT was realized under mild laser irradiation (0.3 W/cm<sup>2</sup> ). The developed strategy for the synthesis of CuS hydrogel provides a novel way to utilize commercial metal sulfides for diverse biological applications.

**Keywords:** commercial copper sulfide (CuS); alginate; hydrogel; photothermal therapy (PTT); near-infrared II windows
