Massive Intracellular Remodeling of CuS Nanomaterials Produces Nontoxic Bioengineered Structures with Preserved Photothermal Potential

Despite efforts in producing nanoparticles with tightly controlled designs and specific physicochemical properties, these can undergo massive nano–bio interactions bioprocessing upon internalization into cells. These transformations generate adverse biological outcomes premature loss of functional efficacy. Hence, understanding the intracellular fate is a necessary prerequisite for their introduction medicine. Among nanomaterials devoted to theranostics copper sulfide (CuS), which provides outstanding optical properties along easy synthesis low cost. Herein, we performed long-term multiscale study on hollow CuS (CuS NPs) rattle-like iron oxide nanoflowers@CuS core–shell hybrids (IONF@CuS when inside stem cells cancer cells, cultured as spheroids. In spheroids, both NPs IONF@CuS are rapidly dismantled smaller units (day 0 3), hair-like nanostructures generated 9 21). This triggers an adaptation cellular metabolism internalized metals without impacting cell viability, differentiation, or oxidative stress response. Throughout remodeling, IONF-derived magnetism observed, but, surprisingly, photothermal potential preserved, demonstrated by full characterization conversion across process. The maintained efficiency correlated well synchrotron X-ray absorption spectroscopy measurements, evidencing similar chemical phase Cu but not Fe over time. findings evidence that reshape them bioengineered reducing function therapeutic potential.