Mitochondria‐Targeted Bovine Serum Albumin@Copper Sulfide Nanocomposites Conjugated with Rhodamine‐110 Dye for an Enhanced Efficacy of Cancer Photothermal Therapy

Abstract Recently, mitochondria‐targeted photothermal nanoagents demonstrated an improved therapeutic efficacy of cancer cells, compared with non‐targeting ones. Herein, copper sulfide (CuS) nanoparticles are in situ synthesized via bovine serum albumin (BSA) templates to prepare photothermal BSA@CuS nanocomposites with high efficiency (42.0%) of photothermal conversion. Subsequently, rhodamine‐110 (R) molecules are covalently conjugated with BSA@CuS nanocomposites to construct mitochondria‐targeted R‐BSA@CuS nanocomposites, which still retained 22.8% of photothermal conversion efficiency. Furthermore, as‐prepared R‐BSA@CuS nanocomposites can be efficiently internalized by human breast cancer (MCF‐7) cells, and then specifically accumulated in their subcellular mitochondria, not lysosomes. Compared with non‐targeting BSA@CuS nanocomposites, these mitochondria‐targeted R‐BSA@CuS nanocomposites show a significant enhancement (*** p < 0.001) of their anticancer efficacy under the same near‐infrared irradiation conditions, whose mechanism is further explored in details. Finally, these R‐BSA@CuS nanocomposites can succeed in penetrating in 3D multicellular tumor spheroids composed of MCF‐7 cells. And they also show a significant inhibition effect (** p < 0.01) on the growth of spheroids via photothermal therapy, in contrast to bare BSA@CuS nanocomposites under the same irradiation conditions. Therefore, these mitochondria‐targeted and photothermal R‐BSA@CuS nanocomposites have important potential applications on cancer photothermal therapy with an enhanced efficacy.