Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases

Jingqin Chen; Rui Chen; Calvin V. Chau; Adam C. Sedgwick; Qiang Xue; Tao Chen; Silue Zeng; Ningbo Chen; Kenneth k. y. Wong; Liang Song; Yaguang Ren; Jian Yang; Jonathan l. Sessler; Chengbo Liu

doi:10.1021/jacs.3c11666

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases

Jingqin Chen, Rui Chen, Calvin V. Chau, Adam C. Sedgwick, Qiang Xue, Tao Chen, Silue Zeng, Ningbo Chen, Kenneth k. y. Wong, Liang Song, Yaguang Ren, Jian Yang, Jonathan l. Sessler, Chengbo Liu

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
Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610064, China
Department of Chemistry, The University of Texas at Austin, 105 East 24th Street-A5300, Austin, Texas 78712-1224, United States
Department of Chemistry, Kings College London, 7 Trinity Street, London SE1 1DB, U.K.
Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong 999077, China
Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou 510280, China

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Abstract

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.

Original language	English
Pages (from-to)	4620-4631
Number of pages	12
Journal	Journal of the American Chemical Society
Volume	146
Issue number	7
DOIs	https://doi.org/10.1021/jacs.3c11666
Publication status	Published - 8 Feb 2024

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Targeted Cyclo[8]pyrrole-based_CHEN_2024_GREEN AAMAccepted author manuscript, 2.95 MB

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Chen, J., Chen, R., Chau, C. V., Sedgwick, A. C., Xue, Q., Chen, T., Zeng, S., Chen, N., Wong, K. K. Y., Song, L., Ren, Y., Yang, J., Sessler, J. L., & Liu, C. (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), 4620-4631. https://doi.org/10.1021/jacs.3c11666

@article{05cb4c1ed52c4a32a2ccc551968c3419,

title = "Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases",

abstract = "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.",

author = "Jingqin Chen and Rui Chen and Chau, {Calvin V.} and Sedgwick, {Adam C.} and Qiang Xue and Tao Chen and Silue Zeng and Ningbo Chen and Wong, {Kenneth k. y.} and Liang Song and Yaguang Ren and Jian Yang and Sessler, {Jonathan l.} and Chengbo Liu",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",

year = "2024",

month = feb,

day = "8",

doi = "10.1021/jacs.3c11666",

language = "English",

volume = "146",

pages = "4620--4631",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "7",

}

Chen, J, Chen, R, Chau, CV, Sedgwick, AC, Xue, Q, Chen, T, Zeng, S, Chen, N, Wong, KKY, Song, L, Ren, Y, Yang, J, Sessler, JL & Liu, C 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, vol. 146, no. 7, pp. 4620-4631. https://doi.org/10.1021/jacs.3c11666

TY - JOUR

T1 - Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases

AU - Chen, Jingqin

AU - Chen, Rui

AU - Chau, Calvin V.

AU - Sedgwick, Adam C.

AU - Xue, Qiang

AU - Chen, Tao

AU - Zeng, Silue

AU - Chen, Ningbo

AU - Wong, Kenneth k. y.

AU - Song, Liang

AU - Ren, Yaguang

AU - Yang, Jian

AU - Sessler, Jonathan l.

AU - Liu, Chengbo

N1 - Funding Information: 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. Publisher Copyright: © 2024 American Chemical Society.

PY - 2024/2/8

Y1 - 2024/2/8

N2 - 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.

AB - 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.

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U2 - 10.1021/jacs.3c11666

DO - 10.1021/jacs.3c11666

M3 - Article

SN - 0002-7863

VL - 146

SP - 4620

EP - 4631

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 7

ER -

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases

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