Developing NIR-II active nanocrystals for biomedical applications
Embargo Date
2027-06-09
OA Version
Citation
Abstract
The second near-infrared (NIR-II, 1000–1700 nm) window enables high-contrast in vivo imaging with deep tissue penetration due to reduced tissue scattering and autofluorescence. Realizing its potential requires the development of high-performance exogenous optical contrast agents. Inorganic semiconductor nanocrystals, including direct bandgap quantum dots (QDs) and carrier-doped plasmonic nanocrystals, shine with tunable and exceptional optical properties for NIR-II applications. This thesis presents the works that bridge nanocrystal design and NIR-II bioimaging applications, with a focus on refining nanomaterial development for better preclinical applications. In Aim 1, we developed high-quality PbS/CdS QDs with tunable NIR-II emissions that enabled imaging of lymphatic networks and visualization of lymphatic drainage. Furthermore, using three QDs with distinct emission profiles, we demonstrated three-color multiplexed imaging of lymphatic and vascular systems simultaneously in live mice. In Aim 2, copper chalcogenide nanocrystals including CuInS2 QDs, plasmonic Cu(2-x)S and CuFeS2 nanocrystals were systematically studied to investigate the relationship between degradation and toxicity. We developed a quantitative method to assess nanocrystals degradation and identified that rapid indium release, triggered by lysosomal environment, was the key factor contributing to CuInS2 toxicity and necrotic cell death. Further modification of surface coating could effectively reduce degradation speed and therefore mitigate the toxicity of nanocrystals. In Aim 3, we designed and synthesized biostable PbS/CdS/ZnS QDs to realize non-invasive tracking of pharmacokinetics and biodistribution through in vivo longitudinal imaging and elemental validation. In contrast, the surprising rapid degradation of PbS/CdS QDs compromised their structural and optical integrity, making them unsuitable for quantitative imaging in vascular circulation. Overall, this work provides a framework and examples for designing NIR-II nanocrystals that integrate biostability and optical properties for bioimaging. We also demonstrated multiplexed and semi-quantitative longitudinal imaging that were enabled by novel high-quality QDs, paving the way for future biomedical applications.
Description
2025