Suhun Chae, Uijung Yong, Wonbin Park, Yoo-mi Choi, In-Ho Jeon, Homan Kang, Jinah Jang, HS Choi, and Dong-Woo Cho. 1/2023. “3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration.” Bioactive Materials, 19, Pp. 611-625. Publisher's Version
H. Kang, M. W. Kang, S. Kashiwagi, and H. S. Choi. 7/20/2022. “NIR fluorescence imaging and treatment for cancer immunotherapy.” Journal for ImmunoTherapy of Cancer, 10, 7, Pp. e004936. Publisher's Version
JunHyun Kim, Minhong Jeong, Wesley R. Stiles, and Haksoo Choi. 5/28/2022. “Neuroimaging Modalities in Alzheimer’s Disease: Diagnosis and Clinical Features.” International Journal of Molecular Sciences, 23, 11, Pp. 6079. Publisher's Version
Xiaoran Yin, Yanan Cui, Richard S. Kim, Wesley R. Stiles, Seung Hun Park, Haoran Wang, Li Ma, Lin Chen, Yoonji Baek, Satoshi Kashiwagi, Kai Bao, Amy Ulumben, Takeshi Fukuda, Homan Kang, and HS Choi. 5/13/2022. “Image-Guided Drug Delivery of Nanotheranostics for Targeted Lung Cancer Therapy.” Theranostics, 12, 9, Pp. 4147-4162. Publisher's Version
Shinya Yokomizo, Maged Henary, Emmanuel R. Buabeng, Takeshi Fukuda, Hailey Monaco, Yoonji Baek, Sophia Manganiello, Jo Kubota, Amy Daniel Ulumben, Xiangmin Lv, Cheng Wang, Kazumasa Inoue, Masahiro Fukushi, Homan Kang, Kai Bao, Satoshi Kashiwagi, and HS Choi. 5/13/2022. “Topical pH Sensing NIR Fluorophores for Intraoperative Ovarian Cancer Imaging and Surgery.” Advanced Science. Publisher's Version
Hailey Monaco, Shinya Yokomizo, Haksoo Choi, and Satoshi Kashiwagi. 5/2022. “Quickly evolving near-infrared photoimmunotherapy provides multifaceted approach to modern cancer treatment.” VIEW, 3, 3, Pp. 20200110. Publisher's VersionAbstract
Abstract Among modalities of cancer immunotherapy, near-infrared photoimmunotherapy (NIR-PIT) has reached significant preclinical and clinical stages and quickly evolved over the last 5 years. NIR-PIT uses deep-penetrable NIR light to induce physicochemical changes in the antibody–photosensitizer conjugate (APC), leading to resultant necrosis and immunogenic cell death (ICD) of the cancer cells. Alternatively, other types of photomedicine use photosensitizers to convert absorbed light energy either into reactive oxygen species for photodynamic therapy (PDT) or into heat for photothermal therapy (PTT). ICD is a unique and relevant outcome of NIR-PIT because it induces long-lasting antitumor host immunity, which overcomes the immunosuppressive network of cancer. Due to its high specificity and durable antitumor effects, NIR-PIT is now considered a promising cancer therapy, and optimized NIR-PIT is readily expanding its applicability to many different types of cancer. Along with the traditional method of NIR-PIT, new avenues in its realm of treatment are currently being explored, such as the targeting of other immunosuppressive elements, delivery of NIR light through a catheter, real-time imaging for tumor detection, and the use of tumor-seeking small molecules for improved efficacy and safety. In addition, its effect on hyperpermeability has opened a door for a wide array of combination therapies with other modalities. This review summarizes the recent findings in clinical and preclinical studies of NIR-induced photomedicine and its future significance in the field of cancer research.
Takeshi Fukuda, Shinya Yokomizo, Stefanie Casa, Hailey Monaco, Sophia Manganiello, Haoran Wang, Xiangmin Lv, Amy Daniel Ulumben, Chengeng Yang, Min-Woong Kang, Kazumasa Inoue, Masahiro Fukushi, Toshiyuki Sumi, Cheng Wang, Homan Kang, Kai Bao, Maged Henary, Satoshi Kashiwagi, and HS Choi. 4/19/2022. “Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores.” Angewandte Chemie International Edition, 61, 17, Pp. e202117330. Publisher's Version
Seung Hun Park, Richard S. Kim, Wesley R. Stiles, Min Joo Jo, Lingxue Zeng, Sunghoon Rho, Yoonji Baek, Jonghan Kim, Moon Suk Kim, Homan Kang, and HS Choi. 3/27/2022. “Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators.” Advanced Science, 9, 15, Pp. 2200872. Publisher's Version
Sungje Bock, Yun-Sik Choi, Minhee Kim, Yewon Yun, Xuan-Hung Pham, Jaehi Kim, Bomi Seong, Wooyeon Kim, Ahla Jo, Kyeong-Min Ham, Sung Gun Lee, Sang Hun Lee, Homan Kang, Haksoo Choi, Dae Hong Jeong, Hyejin Chang, Dong-Eun Kim, and Bong-Hyun Jun. 3/12/2022. “Highly Sensitive Near-Infrared SERS Nanoprobes for In Vivo Imaging using Gold-assembled Silica Nanoparticles with Controllable Nanogaps.” Journal of Nanobiotechnology, 20, Pp. 130. Publisher's Version
Sopida Thavornpradit, Syed Muhammad Usama, G. Kate Park, Jason Dinh, HS Choi, and Kevin Burgess. 3/10/2022. “QuatCy‑I2 and MHI‑I2 in Photodynamic Therapy.” ACS Medicinal Chemistry Letters, 13, 3, Pp. 470-474. Publisher's Version
H. Kang, M. Shamim, X. Yin, E. Adluru, T. Fukuda, S. Yokomizo, H. Chang, S. H. Park, Y. Cui, A. J. Moy, S. Kashiwagi, M. Henary, and H. S. Choi. 1/18/2022. “Tumor-Associated Immune-Cell-Mediated Tumor-Targeting Mechanism with NIR-II Fluorescence Imaging.” Advanced Materials, 34, 8, Pp. 2106500. Publisher's VersionAbstract
The strategy of structure-inherent tumor targeting (SITT) with cyanine-based fluorophores is getting more attention because no chemical conjugation of targeting moieties is required. However, the targeting mechanism behind SITT has not yet been well explained. Here, we demonstrate that heptamethine cyanine-based fluorophores possess not only targetability of tumor microenvironments without the need for additional targeting ligands but also NIR-II imaging capabilities, i.e., minimum scattering and ultralow autofluorescence. The new SITT mechanism suggests that bone-marrow-derived and/or tissue-resident/tumor-associated immune cells can be a principal target for cancer detection due to their abundance in tumoral tissues. Among the tested, SH1 provides ubiquitous tumor targetability and a high tumor-to-background ratio (TBR) ranging from 9.5 to 47 in pancreatic, breast, and lung cancer mouse models upon a single bolus intravenous injection. Furthermore, SH1 can be used to detect small cancerous tissues smaller than 2mm in diameter in orthotopic lung cancer models. Thus, SH1 could be a promising cancer-targeting agent and have a bright future for intraoperative optical imaging and image-guided cancer surgery. This article is protected by copyright. All rights reserved.
A. R. Johnson, M. A. Tetrault, M. G. Bravo, V. Girouard, R. Laurence, B. T. Lee, H. S. Choi, and D. Singhal. 1/1/2022. “Novel Quantification of Real-Time Lymphatic Clearance: Immediate Lymphatic Reconstruction in a Large-Animal Model.” Plastic and reconstructive surgery, 149, 1, Pp. 130-141. Publisher's Version
Chengeng Yang, Haoran Wang, Shinya Yokomizo, Morgan Hickey, Hyejin Chang, Homan Kang, Takeshi Fukuda, Mi Young Song, Sang Yeul Lee, Jin Woo Park, Kai Bao, and Haksoo Choi. 6/14/2021. “ZW800-PEG: A Renal clearable zwitterionic near‐infrared fluorophores for potential clinical translation.” Angew Chem Int Ed Engl, 60, 25, Pp. 13847-13852. Publisher's VersionAbstract
Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. Despite tremendous advances in imaging devices, surprisingly only a few dyes are currently available in the clinic. Previous fluorophores, ZW800-1A and ZW800-1C, significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.
Hye Hyeon Han, Homan Kang, Seong-Jong Kim, Rahul Pal, Anand T. N. Kumar, Haksoo Choi, and Sei Kwang Hahn. 2021. “Fluorescent nanodiamond – hyaluronate conjugates for target-specific molecular imaging.” RSC Adv., 11, Pp. 23073-23081. Publisher's VersionAbstract
Despite wide investigation on molecular imaging contrast agents, there are still strong unmet medical needs to enhance their signal-to background ratio, brightness, photostability, and biocompatibility with multimodal imaging capability. Here, we assessed the feasibility of fluorescent nanodiamonds (FNDs) as carbon based photostable and biocompatible materials for molecular imaging applications. Because FNDs have negatively charged nitrogen vacancy (NV) centers, they can emit bright red light. FNDs were conjugated to hyaluronate (HA) for target-specific molecular imaging. HA is a biocompatible, biodegradable, and linear polysaccharide with abundant HA receptors in the liver, enabling liver targeted molecular imaging. In vitro cell viability tests revealed the biocompatibility of HA–FND conjugates and the competitive cellular uptake test confirmed their target-specific intracellular delivery to HepG2 cells with HA receptors. In addition, in vivo fluorescence lifetime (FLT) assessment revealed the imaging capability of FNDs and HA–FND conjugates. After that, we could confirm the statistically significant liver-targeted delivery of HA–FND conjugates by in vivo imaging system (IVIS) analysis and ex vivo biodistribution tests in various organs. The renal clearance test and histological analysis corroborated the in vivo biocompatibility and safety of HA–FND conjugates. All these results demonstrated the feasibility of HA–FND conjugates for further molecular imaging applications.
Soon Hee Kim, Jin Seon Kwon, Jae Gu Cho, Kate G. Park, Tae Hyeon Lim, Moon Suk Kim, Haksoo Choi, Chan Hum Park, and Sang Jin Lee. 2021. “Non-invasive in vivo monitoring of transplanted stem cells in 3D-bioprinted constructs using near-infrared fluorescent imaging.” Bioengineering & Translational Medicine, 6, 2, Pp. e10216. Publisher's VersionAbstract
Abstract Cell-based tissue engineering strategies have been widely established. However, the contributions of the transplanted cells within the tissue-engineered scaffolds to the process of tissue regeneration remain poorly understood. Near-infrared (NIR) fluorescence imaging systems have great potential to non-invasively monitor the transplanted cell-based tissue constructs. In this study, labeling mesenchymal stem cells (MSCs) using a lipophilic pentamethine indocyanine (CTNF127, emission at 700 nm) as a NIR fluorophore was optimized, and the CTNF127-labeled MSCs (NIR-MSCs) were printed embedding in gelatin methacryloyl bioink. The NIR-MSCs-loaded bioink showed excellent printability. In addition, NIR-MSCs in the 3D constructs showed high cell viability and signal stability for an extended period in vitro. Finally, we were able to non-invasively monitor the NIR-MSCs in constructs after implantation in a rat calvarial bone defect model, and the transplanted cells contributed to tissue formation without specific staining. This NIR-based imaging system for non-invasive cell monitoring in vivo could play an active role in validating the cell fate in cell-based tissue engineering applications.
S. H. Park, H. J. Ju, Y. B. Ji, M. Shah, B. H. Min, H. S. Choi, S. Choi, and M. S. Kim. 2021. “Endogenous Stem Cell-Based In Situ Tissue Regeneration Using Electrostatically Interactive Hydrogel with a Newly Discovered Substance P Analog and VEGF-Mimicking Peptide.” Small, 17, Pp. 2103244.Abstract
The use of chemoattractants to promote endogenous stem cell-based in situ tissue regeneration has recently garnered much attention. This study is the first to assess the endogenous stem cell migration using a newly discovered substance P (SP) analog (SP1) by molecular dynamics simulations as an efficient chemoattractant. Further, a novel strategy based on electrostatic interaction using cationic chitosan (Ch) and anionic hyaluronic acid (HA) to prepare an SP1-loaded injectable C/H formulation without SP1 loss is developed. The formulation quickly forms an SP1-loaded C/H hydrogel in situ through in vivo injection. The newly discovered SP1 is found to possess human mesenchymal stromal cells (hMSCs) migration-inducing ability that is approximately two to three times higher than that of the existing SP. The designed VEGF-mimicking peptide (VP) chemically reacts with the hydrogel (C/H-VP) to sustain the release of VP, thus inducing vasculogenic differentiation of the hMSCs that migrate toward the C/H-VP hydrogel. Similarly, in animal experiments, SP1 attracts a large number of hMSCs toward the C/H-VP hydrogel, after which VP induces vasculogenic differentiation. Collectively, these findings indicate that SP1-loaded C/H-VP hydrogels are a promising strategy to facilitate endogenous stem cell-based in situ tissue regeneration.
H. Lee, Y.H. An, T.K. Kim, J. Ryu, G. K. Park, M.J. Park, J. Ko, H. Kim, H. Choi, Nathaniel S. H., and T.H. Park. 2021. “Enhancement of Wound Healing Efficacy by Increasing the Stability and Skin‐Penetrating Property of bFGF Using 30Kc19α‐Based Fusion Protein.” Advanced Biology, 5, 1, Pp. 2000176. Publisher's Version
Xiaotian Wu, Amy Daniel Ulumben, Steven Long, Wataru Katagiri, Moses Q. Wilks, Hushan Yuan, Brian Cortese, Chengeng Yang, Satoshi Kashiwagi, Haksoo Choi, Marc D. Normandin, Georges El Fakhri, and Raiyan T. Zaman. 2021. “Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model.” Biomolecules, 11, Pp. 1753.
H. G. Moon, S. J. Kim, M. K. Lee, H. Kang, H. S. Choi, A. Harijith, J. Ren, V. Natarajan, J. W. Christman, S. J. Ackerman, and G. Y. Park. 2020. “Colony-stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma.” Allergy, 75, Pp. 357-369.Abstract
BACKGROUND: A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation. OBJECTIVE: To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens. METHODS: We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe. RESULTS: Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction. CONCLUSION: The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.
G. Jones, S. K. Goswami, H. Kang, H. S. Choi, and J. Kim. 2020. “Combating iron overload: a case for deferoxamine-based nanochelators.” Nanomedicine, 15, 13, Pp. 1341-1356.Abstract
While iron is a nutrient metal, iron overload can result in multiple organ failures. Iron chelators, such as deferoxamine, are commonly used to ameliorate iron overload conditions. However, their uses are limited due to poor pharmacokinetics and adverse effects. Many novel chelator formulations have been developed to overcome these drawbacks. In this review, we have discussed various nanochelators, including linear and branched polymers, dendrimers, polyrotaxane, micelles, nanogels, polymeric nanoparticles and liposomes. Although these research efforts have mainly been focused on nanochelators with longer half-lives, prolonged residence of polymers in the body could raise potential safety issues. We also discussed recent advances in nanochelation technologies, including mechanism-based, long-acting nanochelators.