About the lab
PI: Hak Soo Choi
Dr. Choi’s laboratory focuses on the development of novel contrast agents for tissue- and organ-specific targeting and diagnosis. Of particular interest is “Structure-Inherent Targeting,” where small molecules can be used for targeting, imaging, diagnosis and therapy by specifically visualizing target tissue with high optical properties and by avoiding nonspecific uptake in normal background tissues.
Targeted Contrast Agents
Targeted fluorophores can be used for image-guided surgery by specifically visualizing target tissue with high optical properties while avoiding nonspecific uptake in normal background tissues. We have been systematically probing the relationship among the hydrodynamic diameter, shape, charge, and hydrophobicity of contrast agents on their in vivo biodistribution and clearance.
We recently developed a new pharmacophore design strategy called “structure-inherent targeting,” where tissue- and/or organ-specific targeting is engineered directly into the non-resonant structure of NIR fluorophores, thus creating the most compact optical contrast agents as possible for biomedical imaging.
To accelerate the development and clinical translation of promising novel therapeutic agents, we are currently working to translate our tissue-specific nuclear-NIR agents into the clinic by augmenting the polymethine and oxazine chemical scaffolds with PET and SPECT radiolabels for both noninvasive preclinical imaging and intraoperative image-guided surgery.
Image-Guided Drug Delivery
Nanotherapeutics: We have developed nonsticky and renal clearable theranostic nanoparticles (a.k.a. H-Dots) to enable imaging tumors less than 1 cm. H-Dots not only target gastrointestinal stromal tumors (GIST) for image-guided surgery, but also tailor the fate of anticancer drugs such as imatinib (IM) to the tumor site resulting in efficient treatment of unresectable GIST. More importantly, IM-loaded H-Dots exhibit lower uptake into the immune system, improved tumor selectivity, and increased tumor suppression compared to free IM, which accumulates in the spleen/liver.
Chelation Therapy: we developed iron chelator-coated ultrasmall nanochelators that can capture iron from plasma without distributing into non-target tissues and leave the body through urinary excretion. Our renal clearable nanochelators can decrease iron burden and reduce the risk of iron-mediated organ toxicity, with no overt chelator-related side effects.
Our group successfully established (1) near-infrared imaging technology of immune components including vaccines and exosomes to improve immunotherapy and (2) molecular imaging of cancer signaling to develop a novel targeted cancer therapy. We are also working to establish safe, effective, simple, and affordable immunotherapy for infectious diseases, allergy, autoimmune diseases, and cancer using near-infrared laser technology.
Immunotherapy imaging: Recently, we demonstrated the size-dependent transportation of vaccine from injection sites to the secondary lymphoid tissues using a multispectral near-infrared imaging platform. In this program we aim to develop novel technology that can be used to optimize formulation and evaluate the safety of vaccines and immunotherapeutics.
Immuno-oncology imaging: We established a reliable imaging method with a high signal-to-background ratio using TLR4 antibody conjugated with a renal clearable zwitterionic near-infrared fluorophore. In this project, we were able to image liver cancer in real-time after a single intravenous injection of TLR4-targeted near-infrared fluorophores over the period of 3 days under the NIR fluorescence imaging system.
Laser adjuvant technology: We have shown that skin treatment with near-infrared laser light boosts the immune response to vaccine. This “laser adjuvant” is free from cold-chain storage, hypodermic needles, biohazardous sharp waste, irreversible formulation with vaccine antigen, undesirable biodistribution in vital organs or unknown long-term toxicity
Immune-function imaging: We developed a new optical platform equipped with two distinct wavelengths of lasers to realize high-throughput single-cell live immune cell imaging. We successfully observed mitochondrial retrograde signaling including intracellular calcium and reactive oxygen species (ROS) in the large number of T cells simultaneously.
Our BENMD Program took the lead in imaging system development and invented multispectral and multiscale near-infrared fluorescence imaging systems that permit anatomy and function to be visualized simultaneously in real-time, with high sensitivity and no moving parts. These systems provide complete image guidance to surgeons during tumor resection and other surgeries in which a tissue target must be detected, assessed, or resected.
NIR-I imaging system (K-FLARE): The K-FLARE and FIAT-L imaging systems are investigational NIR-I imaging devices allowing simultaneous real-time fluorescence (700 nm and 800 nm) and color imaging (400-650 nm) using laser light (Class 3R) and a dual channel CCD camera. The imaging system kit is not intended for human use, but for non-diagnostic, non-therapeutic, laboratory research use only.
Mesoscale imaging and NIR-II imaging: The Mesoscale Imaging System (MIS) allows real-time concurrent color imaging and two independent NIR fluorescence imaging channels.
Our final goal is to translate our bioimaging technology to the clinic. Based on the first principles of chemistry, engineering, and biology, we have defined the relationship among the key independent variables of targeted fluorophores that dictate biodistribution and tissue-specific targeting in various animal models including mice, rats, and pigs.
We produced high-purity heptamethine indocyanines for large animal and human studies using cGMP-compatible processes (10 g scale; ≈ 1,000 patient doses) through facile and efficient solvent purification, without the need for column chromatography.
We are currently attempting simultaneous targeting of cancerous tissue and vasculature/nerve, or cartilage/bone and vessel/nerve using dual-channel intraoperative imaging, which lays the foundation for clinical translation to image-guided surgery and longitudinal/noninvasive imaging of tissue constructs.
- Yin X, Cheng Y, Feng Y, Stiles WR, Park SH, Kang H, Choi HS. Phototheranostics for multifunctional treatment of cancer with fluorescence imaging. Adv Drug Deliv Rev 2022 189 ():114483
- Wang H, Kang H, Dinh J, Yokomizo S, Stiles WR, Tully M, Cardenas K, Srinivas S, Ingerick J, Ahn S, Bao K, Choi HS. P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging. Biomater Res 2022 26 (1):51
- Kang H, Kang MW, Kashiwagi S, Choi HS. NIR fluorescence imaging and treatment for cancer immunotherapy. J Immunother Cancer 2022 10 (7)
- Kim J, Jeong M, Stiles WR, Choi HS. Neuroimaging Modalities in Alzheimer’s Disease: Diagnosis and Clinical Features. Int J Mol Sci 2022 23 (11)
- Yin X, Cui Y, Kim RS, Stiles WR, Park SH, Wang H, Ma L, Chen L, Baek Y, Kashiwagi S, Bao K, Ulumben A, Fukuda T, Kang H, Choi HS. Image-guided drug delivery of nanotheranostics for targeted lung cancer therapy. Theranostics 2022 12 (9):4147-4162
- Yokomizo S, Henary M, Buabeng ER, Fukuda T, Monaco H, Baek Y, Manganiello S, Wang H, Kubota J, Ulumben AD, Lv X, Wang C, Inoue K, Fukushi M, Kang H, Bao K, Kashiwagi S, Choi HS. Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer. Adv Sci (Weinh) 2022 9 (20):e2201416
- Park SH, Kim RS, Stiles WR, Jo M, Zeng L, Rho S, Baek Y, Kim J, Kim MS, Kang H, Choi HS. Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators. Adv Sci (Weinh) 2022 ():e2200872
- Kang H, Shamim M, Yin X, Adluru E, Fukuda T, Yokomizo S, Chang H, Park SH, Cui Y, Moy AJ, Kashiwagi S, Henary M, Choi HS. Tumor-Associated Immune-Cell-Mediated Tumor-Targeting Mechanism with NIR-II Fluorescence Imaging. Adv Mater 2022 34 (8):e2106500
- Wu X, Daniel Ulumben A, Long S, Katagiri W, Wilks MQ, Yuan H, Cortese B, Yang C, Kashiwagi S, Choi HS, Normandin MD, El Fakhri G, Zaman RT. Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model. Biomolecules 2021 11 (12):
- Yang C, Wang H, Yokomizo S, Hickey M, Chang H, Kang H, Fukuda T, Song MY, Lee SY, Park JW, Bao K, Choi HS. ZW800-PEG: A Renal Clearable Zwitterionic Near-Infrared Fluorophore for Potential Clinical Translation. Angew Chem Int Ed Engl 2021 60 (25):13847-13852
- Ji Y, Jones C, Baek Y, Park GK, Kashiwagi S, Choi HS. Near-infrared fluorescence imaging in immunotherapy. Adv Drug Deliv Rev 2020 167 ():121-134
- Park GK, Lee JH, Soriano E, Choi M, Bao K, Katagiri W, Kim DY, Paik JH, Yun SH, Frangioni JV, Clancy TE, Kashiwagi S, Henary M, Choi HS. Rapid and Selective Targeting of Heterogeneous Pancreatic Neuroendocrine Tumors. iScience 2020 23 (4):101006
- Choi HS, Kim HK. Multispectral image-guided surgery in patients. Nat Biomed Eng 2020 4 (3):245-246
- Lee JH, Jung SY, Park GK, Bao K, Hyun H, El Fakhri G, Choi HS. Fluorometric Imaging for Early Diagnosis and Prognosis of Rheumatoid Arthritis. Adv Sci (Weinh) 2020 7 (1):1902267
- Katagiri W, Lee G, Tanushi A, Tsukada K, Choi HS, Kashiwagi S. High-throughput single-cell live imaging of photobiomodulation with multispectral near-infrared lasers in cultured T cells. J Biomed Opt 2020; 25(3):1-18
View in: PubMed
- Kang H, Stiles WR, Baek Y, Nomura S, Bao K, Hu S, Park GK, Jo MJ, I H, Coll JL, Rubin BP, Choi HS. Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors. Adv Mater 2020 32 (6):e1905899
- Kang H, Rho S, Stiles WR, Hu S, Baek Y, Hwang DW, Kashiwagi S, Kim MS, Choi HS. Size-Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting. Adv Healthc Mater 2020 9 (1):e1901223
- Ji Y, Wang Z, Bao K, Park GK, Kang H, Hu S, McDonald E, Kim MS, Kashiwagi S, Choi HS. Targeted molecular imaging of TLR4 in hepatocellular carcinoma using zwitterionic near-infrared fluorophores. Quant Imaging Med Surg 2019 9 (9):1548-1555
- Yang C, Park GK, McDonald EJ, Choi HS. Targeted Near-Infrared Fluorescence Imaging for Regenerative Medicine. Tissue Eng Regen Med 2019 16 (5):433-442
- Das P, Santos S, Park GK, Hoseok I, Choi HS. Real-Time Fluorescence Imaging in Thoracic Surgery. Korean J Thorac Cardiovasc Surg 2019 52 (4):205-220
- Sajedi S, Sabet H, Choi HS. Intraoperative biophotonic imaging systems for image-guided interventions. Nanophotonics 2019 8 (1):99-116
- Kang H, Hu S, Cho MH, Hong SH, Choi Y, Choi HS. Theranostic Nanosystems for Targeted Cancer Therapy. Nano Today 2018 23 ():59-72
- Park GK, Lee JH, Levitz A, El Fakhri G, Hwang NS, Henary M, Choi HS. Lysosome-Targeted Bioprobes for Sequential Cell Tracking from Macroscopic to Microscopic Scales. Adv Mater 2019 31 (14):e1806216
- Son J, Yi G, Yoo J, Park C, Koo H, Choi HS. Light-responsive nanomedicine for biophotonic imaging and targeted therapy. Adv Drug Deliv Rev 2019 138 ():133-147
- Wada H, Hyun H, Bao K, Lee JH, El Fakhri G, Choi Y, Choi HS. Multivalent Mannose-Decorated NIR Nanoprobes for Targeting Pan Lymph Nodes. Chem Eng J 2018 340 ():51-57
- Hu S, Kang H, Baek Y, El Fakhri G, Kuang A, Choi HS. Real-Time Imaging of Brain Tumor for Image-Guided Surgery. Adv Healthc Mater 2018 7 (16):e1800066
- Park GK, Hoseok , Kim GS, Hwang NS, Choi HS. Optical spectroscopic imaging for cell therapy and tissue engineering. Appl Spectrosc Rev 2018 53 (2-4):360-375
- Bao K, Lee JH, Kang H, Park GK, El Fakhri G, Choi HS. PSMA-targeted contrast agents for intraoperative imaging of prostate cancer. Chem Commun (Camb) 2017 53 (10):1611-1614
- Koo H, Lee JH, Bao K, Wu Y, El Fakhri G, Henary M, Yun SH, Choi HS. Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation. Adv Healthc Mater 2016 5 (19):2510-2516
- Owens EA, Henary M, El Fakhri G, Choi HS. Tissue-Specific Near-Infrared Fluorescence Imaging. Acc Chem Res 2016 49 (9):1731-40
- Ashitate Y, Levitz A, Park MH, Hyun H, Venugopal V, Park G, El Fakhri G, Henary M, Gioux S, Frangioni JV, Choi HS. Endocrine-specific NIR fluorophores for adrenal gland targeting. Chem Commun (Camb) 2016 52 (67):10305-8
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