Sanghwa Jeong†, Jaejung Song‡, Wonseok Lee†, Yeon Mi Ryu§, Yebin Jung†, Sang-Yeob Kim§#, Kangwook Kim†¶, Seong Cheol Hong†, Seung Jae Myung§#⊥, and Sungjee Kim*†‡
†Department of Chemistry and ‡School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), San 31, Hyojadong, Nam-gu, Pohang 37673, South Korea
§ Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
# Department of Convergence Medicine, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
¶ Department of Civil and Environmental Engineering, Korea Army Academy at Young-cheon, Yeongcheon-si, Gyeongsangbuk-do South Korea
⊥ Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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.
Keywords: activatable probe; cancer microenvironment; molecular imaging; quantum dot; Second near-infrared window