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
G. R. Shin, H. E. Kim, H. J. Ju, J. H. Kim, S. Choi, H. S. Choi, and M. S. Kim. 12/2022. “Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative breast cancer.” Mater Today Bio, 16, Pp. 100386. Publisher's VersionAbstract
Triple-negative breast cancer (TNBC) patients are considered intractable, as this disease has few effective treatments and a very poor prognosis even in its early stages. Here, intratumoral therapy with resveratrol (Res), which has anticancer and metastasis inhibitory effects, was proposed for the effective treatment of TNBC. An injectable Res-loaded click-crosslinked hyaluronic acid (Res-Cx-HA) hydrogel was designed and intratumorally injected to generate a Res-Cx-HA depot inside the tumor. The Res-Cx-HA formulation exhibited good injectability into the tumor tissue, quick depot formation inside the tumor, and the depot remained inside the injected tumor for extended periods. In vivo formed Res-Cx-HA depots sustained Res inside the tumor for extended periods. More importantly, the bioavailability and therapeutic efficacy of Res remained almost exclusively within the tumor and not in other organs. Intratumoral injection of Res-Cx-HA in animal models resulted in significant negative tumor growth rates (i.e., the tumor volume decreased over time) coupled with large apoptotic cells and limited angiogenesis in tumors. Therefore, Res-Cx-HA intratumoral injection is a promising way to treat TNBC patients with high efficacy and minimal adverse effects.
Jason Dinh, Atsushi Yamashita, Homan Kang, Sylvain Gioux, and H. S. Choi. 10/13/2022. “Optical Tissue Phantoms for Quantitative Evaluation of Surgical Imaging Devices.” Advanced Photonics Research. Publisher's Version
Haoran Wang, Homan Kang, Jason Dinh, Shinya Yokomizo, Wesley R. Stiles, Molly Tully, Kevin Cardenas, Surbhi Srinivas, Jason Ingerick, Sung Ahn, Kai Bao, and H. S. Choi. 10/1/2022. “P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging.” Biomaterials Research, 26, Pp. 51. Publisher's Version
X. Yin, Y. Cheng, Y. Feng, W. R. Stiles, S. H. Park, H. Kang, and H. S. Choi. 10/2022. “Phototheranostics for Multifunctional Treatment of Cancer with Fluorescence Imaging.” Adv Drug Deliv Rev, 189, Pp. 114483. Publisher's VersionAbstract
Phototheranostics stem from the recent advances in nanomedicines and bioimaging to diagnose and treat human diseases. Since tumors' diversity, heterogeneity, and instability limit the clinical application of traditional diagnostics and therapeutics, phototheranostics, which combine light-induced therapeutic and diagnostic modalities in a single platform, have been widely investigated. Numerous efforts have been made to develop phototheranostics for efficient light-induced antitumor therapeutics with minimal side effects. Herein, we review the fundamentals of phototheranostic nanomedicines with their biomedical applications. Furthermore, the progress of near-infrared fluorescence imaging and cancer treatments, including photodynamic therapy and photothermal therapy, along with chemotherapy, immunotherapy, and gene therapy, are summarized. This review also discusses the opportunities and challenges associated with the clinical translation of phototheranostics in pan-cancer research. Phototheranostics can pave the way for future research, improve the quality of life, and prolong cancer patients' survival times.
Hyehee Kim, Jianlin Li, Anthony Childress, Juyeon Seo, Poornaprakash Bathalavaram, Ahmed Busnaina, Sung-Hyun Moon, Jihwan Boo, H. S. Choi, Geehyun Kim, Young Lae Kim, and Yung Joon Jung. 9/27/2022. “Ultralow-Power and Miniaturized X-ray Sensor Using the Single-Walled Carbon Nanotube Micro Network-Based Geiger Counter Design.” ACS Applied Electronic Materials, 4, Pp. 4823-4830. Publisher's Version
W. Katagiri, S. Yokomizo, T. Ishizuka, K. Yamashita, T. Kopp, M. Roessing, A. Sato, T. Iwasaki, H. Sato, T. Fukuda, H. Monaco, S. Manganiello, S. Nomura, M. R. Ng, S. Feil, E. Ogawa, D. Fukumura, D. N. Atochin, H. S. Choi, and S. Kashiwagi. 9/2/2022. “Dual near-infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy.” FASEB J, 36, Pp. e22521. Publisher's VersionAbstract
Immunotherapy, including immune checkpoint inhibitors, has revolutionized cancer treatment, but only a minor fraction of patients shows durable responses. A new approach to overcome this limitation is yet to be identified. Recently, we have shown that photobiomodulation (PBM) with near-infrared (NIR) light in the NIR-II window reduces oxidative stress and supports the proliferation of CD8(+) T cells, suggesting that PBM with NIR-II light could augment anti-cancer immunity. Here, we report a novel approach to support tumor-infiltrating CD8(+) T cells upon PBM with NIR-II laser with high tissue penetration depth. Brief treatments of a murine model of breast cancer with dual 1064 and 1270 nm lasers reduced the expression of the programmed cell death protein 1 (PD-1) in CD8(+) T cells in a syngeneic mouse model of breast cancer. The direct effect of the NIR-II laser treatment on T cells was confirmed by the enhanced tumor growth delay by the adoptive transfer of laser-treated CD8(+) T cells ex vivo against a model tumor antigen. We further demonstrated that specific NIR-II laser parameters augmented the effect of the immune checkpoint inhibitor on tumor growth. PBM with NIR-II light augments the efficacy of cancer immunotherapy by supporting CD8(+) T cells. Unlike the current immunotherapy with risks of undesirable drug-drug interactions and severe adverse events, the laser is safe and low-cost. It can be broadly combined with other therapy without modification to achieve clinical significance. In addition, our study established a path to develop a novel laser-based therapy to treat cancer effectively.
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
S. Ekaputri, E. K. Choi, M. Sabelli, L. Aring, K. J. Green, J. Chang, K. Bao, H. S. Choi, S. Iwase, J. Kim, E. Corradini, A. Pietrangelo, M. D. Burke, and Y. A. Seo. 6/22/2022. “A small molecule redistributes iron in ferroportin-deficient mice and patient-derived primary macrophages.” Proc Natl Acad Sci U S A, 119, 26, Pp. e2121400119. Publisher's VersionAbstract
Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause the iron misdistribution that underlies ferroportin disease, anemia of inflammation, and several other human diseases and conditions. A small molecule natural product, hinokitiol, was recently shown to serve as a surrogate transmembrane iron transporter that can restore hemoglobinization in zebrafish deficient in other iron transporting proteins and can increase gut iron absorption in FPN1-deficient flatiron mice. However, whether hinokitiol can restore normal iron physiology in FPN1-deficient animals or primary cells from patients and the mechanisms underlying such targeted activities remain unknown. Here, we show that hinokitiol redistributes iron from the liver to red blood cells in flatiron mice, thereby increasing hemoglobin and hematocrit. Mechanistic studies confirm that hinokitiol functions as a surrogate transmembrane iron transporter to release iron trapped within liver macrophages, that hinokitiol-Fe complexes transfer iron to transferrin, and that the resulting transferrin-Fe complexes drive red blood cell maturation in a transferrin-receptor-dependent manner. We also show in FPN1-deficient primary macrophages derived from patients with ferroportin disease that hinokitiol moves labile iron from inside to outside cells and decreases intracellular ferritin levels. The mobilization of nonlabile iron is accompanied by reductions in intracellular ferritin, consistent with the activation of regulated ferritin proteolysis. These findings collectively provide foundational support for the translation of small molecule iron transporters into therapies for human diseases caused by iron misdistribution.
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.
R. Cheng, R. Gadde, Y. Fan, N. Kulkarni, N. Shevale, K. Bao, H. S. Choi, S. Betharia, and J. Kim. 4/21/2022. “Reversal of genetic brain iron accumulation by N,N'-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice.” Arch Toxicol, 96, Pp. 1951-1962. Publisher's VersionAbstract
N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic metal chelator and antioxidant used in mercury poisoning. Recent studies have suggested that NBMI may also bind to other metals such as lead and iron. Since NBMI can enter the brain, we evaluated if NBMI removes excess iron from the iron-loaded brain and ameliorates iron-induced oxidative stress. First, NBMI exhibited preferential binding to ferrous (Fe(2+)) iron with a negligible binding affinity to ferric (Fe(3+)) iron, indicating a selective chelation of labile iron. Second, NBMI protected SH-SY5Y human neuroblastoma cells from the cytotoxic effects of high iron. NBMI also decreased cellular labile iron and lessened the production of iron-induced reactive oxygen species in these cells. Deferiprone (DFP), a commonly used oral iron chelator, failed to prevent iron-induced cytotoxicity or labile iron accumulation. Next, we validated the efficacy of NBMI in Hfe H67D mutant mice, a mouse model of brain iron accumulation (BIA). Oral gavage of NBMI for 6 weeks decreased iron accumulation in the brain as well as liver, whereas DFP showed iron chelation only in the liver, but not in the brain. Notably, depletion of brain copper and anemia were observed in BIA mice treated with DFP, but not with NBMI, suggesting a superior safety profile of NBMI over DFP for long-term use. Collectively, our study demonstrates that NBMI provides a neuroprotective effect against BIA and has therapeutic potential for neurodegenerative diseases associated with BIA.
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