김종승 (고려대학교)

한빛사논문

조회161

고려대학교

J. Am. Chem. Soc., Jul 03 2024, | https://doi.org/10.1021/jacs.4c05978 Lutetium Texaphyrin-Celecoxib Conjugate as a Potential Immuno-Photodynamic Therapy Agent

Jusung An ¹, Kong-Peng Lv ^2,3, Calvin V Chau ⁴, Jong Hyeon Lim⁵, Rakesh Parida ⁵, Xin Huang ², Snehasish Debnath ¹, Yunjie Xu¹, Siqi Zheng³, Adam C Sedgwick⁴, Jin Yong Lee ⁵, Dixian Luo ², Quan Liu ², Jonathan L Sessler ⁴, Jong Seung Kim ¹

¹Department of Chemistry, Korea University, Seoul 02841, Korea.

²Laboratory Medicine Center, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Nanshan Avenue, Shenzhen 518000, Guangdong, China.

³Department of Interventional Radiology, Shenzhen People's Hospital, (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.

⁴Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.

⁵Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea.

J.A., K.-P.L., C.V.C., and J.H.L. contributed equally to this work.

Corresponding Authors: Jin Yong Lee, Dixian Luo, Quan Liu, Jonathan L. Sessler, Jong Seung Kim

Abstract

Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O ₂ ^-•) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-05)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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