Near Infrared Luminescent Nanoparticles for Bioimaging

Abstract

High-quality fluorescence imaging of molecules for in vivo clinical and preclinical application has improved with the development of novel near infrared (NIR) luminescent probes. The first near-infrared (NIR-I) window at wavelengths between 700 and 900 nm can guarantee the deep light penetration and minimal autofluorescence. Quantum dots (QDs) are a well-suited nano-emitter that can be bright and easily multiplexed at the NIR window. Lanthanide doped nanoparticles (La NPs) can also have the emissions at the NIR window via upconversion process. A new multiplexed NIR in vivo Imaging is showcased by complementarily using QDs and La NPs. In addition to the QD multiplexing, ‘temporal’ multiplexing is implemented by alternating the excitation wavelengths and unmixing the QD and La NP emissions. The multiplexed imaging is successfully obtained for cellular labeling and cellular trafficking in small animal models. CdTeSe QDs and NaYF4:20%Yb3+, 2%Tm3+ La NPs are used for the multiplexed imaging, and extensively characterized including the extinction coefficients. Despite of the notable discrepancy in the emission mechanisms, QDs and La NPs can be successfully co-used for multiplexed imaging with both agents in comparable concentrations. High-resolution fluorescence imaging of molecules intrinsically involved in cancer progression and metastasis would be valuable for early detection and staging of tumors. Combining the advantageous features of the second infrared (NIR-II, 1000-1400 nm) window than NIR-I window for minimal light interference from biological tissues and the design of fluorescence activation for sensitive detection of biological event, NIR-II activatable probe sensitive for cancer microenvironment, matrix metalloproteinase (MMP) was developed. At first, lead sulfide-based multishell QD structure, PbS/CdS/ZnS core/shell/shell QDs, was synthesized for highly luminescent NIR-II emitting probe for biological application instead of conventional single-walled carbon nanotubes (SWCNs) of low photoluminescence quantum yield (PL QY) of ~0.1 %. PbS/CdS/ZnS QD, which consisted of thick CdS and thin ZnS inorganic shell, showcased enhanced PL QY of ~10%, and resistance to photobleaching than PbS/CdS QDs, with compact hydrodynamic size of ~10 nm and colloidal stability in aqueous phase. The fluorescence modulation of PbS/CdS/ZnS QDs was enabled by photo-induced electron transfer from QD to methylene blue (MB) in the close proximity. For activatable probe, protease-cleavable peptide sequence, specific to MMP as cancer-related enzyme family, linked PbS/CdS/ZnS QD with fluorescence quencher of MB via covalent crosslinking. The structure of peptide sequence was modified and optimized for efficient activatable probe in the points of charged state and enzyme accessibility. Finally, ex vivo fluoresence imaging with spraying NIR-II activatable probe onto colon cancer model verified the time-dependent tumor-specific signal amplification of activatable probe.