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

## TL;DR

This paper studies how the composition and degradation of copper-based nanocrystals affect their toxicity in biological systems.

## Contribution

The study introduces a quantitative degradation assay and shows how modifying coatings can reduce nanocrystal toxicity.

## Key findings

- CuInS2 and CuFeS2 degrade rapidly in artificial lysosomal fluid, releasing indium and iron ions.
- CuInS2 shows higher cytotoxicity due to indium-induced necrosis compared to Cu2–xS and CuFeS2.
- A modified polymer coating reduces both degradation and toxicity of CuInS2.

## Abstract

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 the 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 two plasmonic semiconductors, copper sulfide (Cu2–x
S) and chalcopyrite copper iron
sulfide (CuFeS2). We developed a quantitative degradation
assay to assess ion release from these ultrasmall nanocrystals, revealing
that while all three particles biodegrade, CuInS2 and CuFeS2 undergo rapid degradation in an artificial lysosomal fluid,
leading to a burst release of indium and iron ions. In cellular toxicity
assays, CuInS2 exhibited a significantly higher acute cytotoxicity
than Cu2–x
S 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 the cytotoxicity of CuInS2. These findings highlight the influence of both nanocrystal
composition and coating chemistry in moderating the acute cytotoxicity
of degradable nanocrystals, demonstrating that tuning of composition
and degradation rate can be used to moderate nanoparticle toxicity.