Cancer-Microenvironment-Sensitive Activatable Quantum Dot Probe in the Second Near-Infrared Window

Abstract

Recent technological advances have expanded fluorescence (FL) imaging into the second near-infrared region (NIR-II; wavelength = 1000-1700 nm), providing high spatial resolution through deep tissues. However, bright and compact fluorophores are rare in this region, and sophisticated control over NIR-II probes has not been fully achieved yet. Herein, we report an enzyme-activatable NIR-II probe that exhibits FL upon matrix metalloprotease activity in tumor microenvironment. Bright and stable PbS/CdS/ZnS core/shell/shell quantum dots (QDs) were synthesized as a model NIR-II fluorophore, and activatable modulators were attached to exploit photoexcited electron transfer (PET) quenching. The quasi type-II QD band alignment allowed rapid and effective FL modulations with the compact surface ligand modulator that contains methylene blue PET quencher. The modulator was optimized to afford full enzyme accessibility and high activation signal surge upon the enzyme activity. Using a colon cancer mouse model, the probe demonstrated selective FL activation at tumor sites with 3-fold signal enhancement in 10 min. Optical phantom experiments confirmed the advantages of the NIR-II probe over conventional dyes in the first near-infrared region.

Biocompatible Semiconductor Quantum Dots as Cancer Imaging Agents

“…The parallel development of improved detectors, 3D deconvolution, spectral unmixing, and reconstruction algorithms will also aid in the adoption of QDs for deeper tissue imaging using fluorescence‐mediated tomography. Long‐term, QD may also serve additional roles such as probes for multiplexed characterization of the tumor microenvironment, targeted drug delivery, photodynamic therapy, or photothermal therapy . Ultimately, the goals of QD design should be to avoid adverse reactions, demonstrate a high preference for tumors or lymph nodes compared to healthy tissue, exhibit strong and stable fluorescence within the near‐infrared biological imaging windows, and be cleared by the body over a duration that is sufficiently long to retain optimal contrast during surgery, but then be completely cleared soon after.…”

Near infrared quantum dots in biomedical applications: current status and future perspective

“…The NIR‐II QDs, which were composed of bright and stable PbS/CdS/ZnS (core/shell/shell) that emit at 1200 nm, have been demonstrated selective imaging at tumor sites by using a colon cancer mouse model. Further optical phantom experiments confirmed the advantages of the NIR‐II QDs over conventional dyes in the first NIR region …”

Advanced Near‐Infrared Light for Monitoring and Modulating the Spatiotemporal Dynamics of Cell Functions in Living Systems

“…The high activity of matrix metalloproteinase (MMP) is known as a hallmark of the cancer microenvironment. [ 64,86,87 ] Recently, Kim and colleagues reported an MMP‐activatable NIR‐II quantum dots (QDs) for tumor detection ( Figure a–d). [ 64 ] In this study, the authors synthesized PbS/CdS/ZnS core/shell/shell QDs with NIR‐II emission.…”