Biogenic copper sulfide nanoaggregates via intracellular-tailoring for enhanced photothermal therapy

Photothermal conversion efficiency and biocompatibility are two valuable factors of photothermal agents for photothermal therapy of tumors. However, the synthesis of efficient photothermal agents with desired biocompatibility remains a great challenge in the green synthesis due to harsh reaction conditions of existing methods. Herein, a green and facile biosynthetic method for preparing the photothermal agent (PTA) copper sulfide by cell-regulated was reported for the first time. The intracellular CuS nanoaggregates (nCuS) are biosynthesized using yeast cells as bioreactors and the functional yeast cells including the intercellular bio-PTA with photothermal effect are constructed (nCuS@yeast). The biomolecules derived from the yeast cells are used as conditioning and stabilizing mediator to regulate the biosynthesis of the nCuS. The biosynthetic nCuS exhibits a good biocompatibility and a high photothermal conversion efficiency (45.24 %). Additionally, the absorption of internal nCuS in the near-infrared region is not affected by the cell wall, which is beneficial for photothermal therapy. <em>In vitro</em> and <em>in vivo </em>studies reveal the great potential of nCuS@yeast in tumor photothermal therapy. This research establishes a new and green avenue for the synthesis of biocompatible photothermal nanomaterials through a cell-based biosynthesis strategy, highlighting its potential application in the field of tumor therapy.