Elemental Composition and Degradation Rate Impact the Biocompatibility of Copper Chalcogenide Nanocrystals

Copper chalcogenide nanocrystals (NCs) are promising candidates for biophotonic applications due to their tunable optical properties. Concrete methods to examine the relationship between their degradation and toxicity are necessary to enable development of nanoconstructs with reduced toxicity. This study compares the degradation and acute cytotoxicity of three compositions of micelle-coated copper chalcogenide NCs: the fluorescent semiconductor copper indium sulfide (CuInS2), and the plasmonic semiconductors copper sulfide (Cu2-xS) and chalcopyrite copper iron sulfide (CuFeS2). We developed a quantitative degradation assay to assess ion release from these ultra-small nanocrystals, revealing that while all three particles biodegrade, CuInS2 and CuFeS2 undergo rapid degradation in artificial lysosomal fluid, leading to a burst release of indium and iron ions. In cellular toxicity assays, CuInS2 exhibited significantly higher acute cytotoxicity than Cu2-xS and CuFeS2, primarily due to indium-induced necrosis. To mitigate this toxicity, an alternative surface-binding polymer coating was introduced, effectively reducing both the degradation rate and cytotoxicity of CuInS2. These findings highlight the influence of both nanocrystal composition and coating chemistry in moderating the acute cytotoxity of degradable nanocrystals, demonstrating that tuning of composition and degradation rate can be used to moderate nanoparticle toxicity.