Research Interests

Therapeutic Nanoplatform

Our research centers on the design of therapeutic nanoplatforms that integrate nanotechnology, near-infrared (NIR) imaging, and immunotherapy to advance precision medicine. We engineer nanomaterials to enhance the targeted delivery and efficacy of small molecules, biologics, and RNA-based therapeutics through precise control of their physicochemical properties. This approach enables optimized biodistribution, reduced systemic toxicity, and spatiotemporally controlled treatment. By leveraging NIR light for deep-tissue molecular imaging, we aim to visualize and modulate immune responses in cancer, infectious diseases, and allergies. Ultimately, our goal is to translate these technologies into safe, effective, and accessible therapies that unify diagnostics and treatment—pioneering a new generation of image-guided immunotherapies and nanomedicines.

(Ji Y et al., Adv Drug Deliv Rev. 2020 Jun 21:S0169-409X(20)30058-2)

Disease Targeting and Mechanism

(Angew Chem Int Ed Engl, 2022; 61(17): e202117330.)

NIR (near-infrared ) Fluorophores

In collaboration with Professor Maged Henary at Georgia State University (GSU), we are developing novel near-infrared (NIR) fluorophores with ultrabright optical properties, favorable pharmacokinetics, and high organ or disease (i.e., tumor and inflammation) selectivity. These fluorophores enable high-contrast and long-lasting NIR imaging for fluorescence-guided cancer surgery and can be administered through both intravenous injection and topical (spray) application, providing versatile options for clinical translation.

(Advanced Materials. 2022;34(8):2106500)

(Biomater Res, 2024; 28:0002)

Immune Cell–Mediated Tumor Targeting

We have discovered a novel tumor-targeting mechanism in which near-infrared (NIR) fluorophores are selectively internalized by bone marrow–derived and tissue-resident immune cells, particularly tumor-associated macrophages (TAMs). These labeled immune cells naturally migrate and accumulate within the tumor microenvironment, effectively acting as biological carriers that transport imaging agents deep into tumors. This immune cell–driven targeting strategy enables noninvasive NIR-II fluorescence visualization of diverse tumor types, including pancreatic, breast, and lung cancers, and establishes a mechanistic foundation for developing next-generation, immune-guided theranostic platforms.

Photodynamic and Photothermal Therapy

We are developing novel near-infrared fluorophores that combine precise tumor targeting with potent phototherapeutic efficacy. Upon low-power laser irradiation, these agents simultaneously trigger photodynamic (PDT) and photothermal (PTT) effects, leading to immunogenic cell death (ICD), dendritic-cell activation, and cytotoxic T-cell recruitment. This synergistic mechanism enhances anti-tumor immunity while minimizing collateral damage, positioning our fluorophores as promising candidates for next-generation, image-guided cancer therapy.

Relevant Publications

Fukuda T, Yokomizo S, Casa S, Monaco H, Manganiello S, Wang H, Lv X, Ulumben AD, Yang C, Kang MW, Inoue K, Fukushi M, Sumi T, Wang C, Kang H, Bao K, Henary M, Kashiwagi S*, Choi HS*. Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores. Angew Chem Int Ed Engl, 2022, 61(17): e202117330.
Yokomizo S, Henary M, Buabeng ER, Fukuda T, Monaco H, Yoonji Baek, Sophia Manganiello, 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 Ovarian Cancer Imaging and Surgery. Adv Sci, 2022, 9(20):e2201416.
Kang H, Kang MW, Kashiwagi S*, Choi HS*. NIR fluorescence imaging and treatment for cancer immunotherapy. J Immunother Cancer, 2022;10(7):e004936.
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.
Kashiwagi S*, Choi HS. Ovarian cancer-targeted near-infrared fluorophores for fluorescence-guided surgery. Ann Transl Med, 2023; 11(6):274.
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.
Ji Y, Jones C, Baek Y, Park GK, Kashiwagi S,* Choi HS.* Near-infrared fluorescence imaging in immunotherapy. Adv Drug Deliv Rev, 2020; S0169-409X(20)30058-2.
Bao K, Tully M, Cardenas K, Wang H, Srinivas S, Rho J, Jeon OH, Dinh J, Yokomizo S, McDonnell R, Yamashita A, Kashiwagi S, Kang H, Kim HK, Choi HS. Ultralow Background Near-infrared Fluorophores with Dual-Channel Intraoperative Imaging Capability. Adv Healthc Mater, 2023 e2203134.
Nomura S, Yokomizo S, Wang Z, Kang H, Bao K, Yang C, Rubin BP, Bronson R, Kashiwagi S, Choi HS. CD117-Targeted Intraoperative Imaging of Gastrointestinal Stromal Tumor Using a Stem-Cell-Factor-Labeled Fluorophore. Adv NanoBiomed Res, 2023 230006.
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 NIR fluorophores. Quant Imaging Med Surg, 2019, 9(9):1548-1555.

Cartilage-Targeting Imaging for Rheumatoid Arthritis

We developed a bone and cartilage-targeting NIR-II fluorophores that achieves high-specificity imaging of bone and cartilage, respectively, with minimal background and low toxicity (Biomater Res, 2022 & Chem, 2025). This probe holds strong translational potential for the early diagnosis of rheumatoid arthritis and other joint diseases, and may further contribute to applications in joint surgery, tissue engineering, and inflammatory disease therapeutics.

Relevant Publications

Kang H et al., Cartilage-targeting fluorophores for early detection of arthritis in the NIR-II window, Chem. 2025;11(8):102481
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.
Chae S, Yong U, Park W, Choi Y-m, Jeon I-H, Kang H, Jang J, Choi HS, Cho D-W. 3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration. Bioact Mater, 2023;19:611-25.

Photomodulation

(Stroke, 2024;55(6):1641-9)

Pretreatment of the brain with a physical parameter, namely a low-power near-infrared (NIR) laser, improves cerebral blood flow and endothelial nitric oxide synthase (eNOS) phosphorylation. Transcranial photobiomodulation (PBM) with NIR laser could offer a non-invasive and low-risk therapy for stroke and Alzheimer’s disease.

Relevant Publications

Katagiri W, Lee GH, Tanushi A, Tsukada K, Choi HS*, Kashiwagi S*. 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
Yokomizo S, Roessing M, Morita A, Kopp T, Ogawa E, Katagiri W, Feil S, Huang PL, Atochin DN, Kashiwagi S*. Near-infrared II photobiomodulation augments nitric oxide bioavailability via phosphorylation of endothelial nitric oxide synthase. FASEB J, 2022 36(9):e22490.
Kashiwagi S*, Morita A, Yokomizo S, Ogawa E, Komai E, Huang PL, Bragin DE, Atochin DN. Photobiomodulation and nitric oxide signaling. Nitric Oxide, 2023; 130:58-68.
Yokomizo S, Kopp T, Roessing M, Morita A, Lee S, Cho S, Ogawa E, Komai E, Inoue K, Fukushi M, Feil S, Kim HH, Bragin DE, Gerashchenko D, Huang PL, Kashiwagi S*, Atochin DN*. Near-infrared II photobiomodulation ameliorates stroke injury via phosphorylation of endothelial nitric oxide synthase. Stroke, 2024 55(6):1641-1649.
Kashiwagi S*, Yokomizo S, Bragin DE, Perle SJ, Kastanenka KV, Gerashchenko D, Atochin DN. Therapeutic Potentials of Near-Infrared II Photobiomodulation to Treat Cerebrovascular Diseases via Nitric Oxide Signaling. Adv Exp Med Biol, 2024;1463:195-200.

Drug Delivery and Scavenging Therapy

Nanoplatforms for targeted therapy and drug delivery

Advances in molecular imaging modalities have accelerated the diagnosis and treatment of human diseases. However, high nonspecific uptake in the major organs and persistent background retention result in a low tumor-to-background ratio. To overcome these issues, we have developed nonsticky and renal clearable theranostic nanoparticles (H-Dots). H-Dots not only target 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. In addition, H-Dots can monitor targetability, pharmacokinetics, and drug delivery, while also showing therapeutic efficacy in GIST-bearing xenograft mice following surgical resection. 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. Precisely designed H-Dots can be used as a promising theranostic nanoplatform that can potentially reduce the side effects of conventional chemotherapies.

Chelation Therapy – Renal Clearable Nanochelators

Iron is an essential nutrient metal, but excess iron is toxic due to increased oxidative stress caused by iron-catalyzed reactive oxygen species. Although several iron chelators are clinically used to reduce iron burden, the use of these chelators is limited due to significant adverse effects likely due to the nonspecific distribution of chelators in off-target tissues. To overcome this challenge, 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.

Relevant Publications

Drug delivery system

Kang H et al., Renal clearable organic nanocarriers for bioimaging and drug delivery, Advanced Materials. 2016;28(37):8162-8
Kang H et al., Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors, Advanced Materials. 2020;32(6):1905899
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):4147-62
Kang H et al., Theranostic nanosystems for targeted cancer therapy, Nano Today. 2018; 23:59-72
Kang H et al., Size‐Size-dependent EPR effect of polymeric nanoparticles on tumor targeting, Advanced Healthcare Materials. 2020;9(1):1901223
Yin X, Cheng Y, Feng Y, Stiles WR, Park SH, Kang H,* Choi HS*. Phototheranostics for Multifunctional Treatment of Cancer with Fluorescence Imaging. Advanced Drug Delivery Reviews. 2022;189:114483
Cui Y, Park SH, Stiles WR, Yamashita A, Dihn J, Kim RS, Zhang Y, Yin X, Baek Y, Wang H, Bao K, Kang H,* Choi HS*. Renal Clearable H‐Dots Leveraging Ligand Complexation for Enhanced Active Tumor Targeting. Small Science. 2024; 4(11), 2400246

Chelation therapy

Kang H et al., Renal clearable nanochelators for iron overload therapy, Nature Communications. 2019;10(1):5134
Park SH, Kim RS, Stiles WR, Jo MJ, Zeng L, Rho S, Baek Y, Kim J, Kim MS, Kang H,* Choi HS*. Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators, Advanced Science. 2022;9(15):e2200872
Jones G, Goswami SK, Kang H, Choi HS, Kim J. Combating iron overload: a case for deferoxamine-based nanochelators. Nanomedicine. 2020;15(13):1341

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