机构：[1]Research Center for Biomedical Optics and Molecular Imaging, Key Laboratory of Biomedical Imaging Science and Systems, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.[2]Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.南方医科大学珠江医院[3]Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou 510280, China.[4]Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610064, China.四川大学华西医院[5]Department of Chemistry, University of Texas at Austin, 105 East 24th Street A5300, Austin, Texas 78712-1224, United States.[6]Department of Chemistry, Kings College London, 7 Trinity Street, London SE1 1DB, U.K.[7]Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong 999077, China.
Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvβ3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.
基金：
The work was supported by grants from the National Key R&D
Program of China (2022YFE0132300, 2023YFF0715300,
2023YFC2411700 to C.L., 2020YFA0908800 to J.C.); the
National Natural Science Foundation of China (82172008 to
J.C., 82122034, 82327805, 81927807 to C.L., 82272132 to J.Y.);
the Youth Innovation Promotion Association, Chinese Academy of Sciences (2023374 to J.C. and 2019352 to C.L.); the
Shenzhen Science and Technology Innovation Grant
(JCYJ20220818101403008 to C.L.); the Key Laboratory of
Biomedical Imaging Science and System, Chinese Academy of
Sciences; Guangdong Provincial Key Laboratory of Biomedical
Optical Imaging (2020B121201010 to J.C.); Shenzhen Key
Laboratory for Molecular Imaging (ZDSY20130401165820357
to L.S.); Basic and Applied Basic Research Foundation of
Guangdong Province (2019A1515110727 to Y.R.). The work in
Austin was supported by the Robert A. Welch Foundation (F-
0018 to J.S.) and by NIH grant RO1 CA68682 subsequent to
June 2022.
第一作者机构：[1]Research Center for Biomedical Optics and Molecular Imaging, Key Laboratory of Biomedical Imaging Science and Systems, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
共同第一作者：
通讯作者：
通讯机构：[2]Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.[3]Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou 510280, China.
推荐引用方式(GB/T 7714)：
Chen Jingqin,Chen Rui,Chau Calvin V,et al.Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases[J].JOURNAL OF THE AMERICAN CHEMICAL SOCIETY.2024,146(7):4620-4631.doi:10.1021/jacs.3c11666.
APA：
Chen Jingqin,Chen Rui,Chau Calvin V,Sedgwick Adam C,Xue Qiang...&Liu Chengbo.(2024).Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,146,(7)
MLA：
Chen Jingqin,et al."Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 146..7(2024):4620-4631
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