A Polymeric Extracellular Matrix Nanoremodeler for Activatable Cancer Photo‐Immunotherapy

Angewandte Chemie International EditionEarly View e202217339 Research Article A Polymeric Extracellular Matrix Nanoremodeler for Activatable Cancer Photo-Immunotherapy Dr. Chi Zhang, Dr. Chi Zhang School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorMengke Xu, Mengke Xu School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorZiling Zeng, Ziling Zeng School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorXin Wei, Xin Wei School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorDr. Shasha He, Dr. Shasha He School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorJingsheng Huang, Jingsheng Huang School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorProf. Kanyi Pu, Corresponding Author Prof. Kanyi Pu kypu@ntu.edu.sg orcid.org/0000-0002-8064-6009 School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921 SingaporeSearch for more papers by this author Dr. Chi Zhang, Dr. Chi Zhang School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorMengke Xu, Mengke Xu School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorZiling Zeng, Ziling Zeng School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorXin Wei, Xin Wei School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorDr. Shasha He, Dr. Shasha He School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorJingsheng Huang, Jingsheng Huang School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 SingaporeSearch for more papers by this authorProf. Kanyi Pu, Corresponding Author Prof. Kanyi Pu kypu@ntu.edu.sg orcid.org/0000-0002-8064-6009 School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921 SingaporeSearch for more papers by this author First published: 24 January 2023 https://doi.org/10.1002/anie.202217339Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract A semiconducting polymer-based extracellular matrix (ECM) remodeler (SPNcb) with photodynamic antitumor activity and inhibition of collagen-crosslinking enzymes is developed for activatable cancer photo-immunotherapy. SPNcb-mediated ECM-remodeling therapy synergizes with checkpoint blockade immunotherapy to reinvigorate cytotoxic T cell-mediated antitumor immunity, inhibiting tumor growth and metastasis. Abstract Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer-based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer-specific inhibition of collagen-crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo-immunotherapy. SPNcb is self-assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β-aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)-cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor-overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis. Conflict of interest The authors declare no conflict of interest. Open Research Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Filename Description anie202217339-sup-0001-misc_information.pdf4.8 MB Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Early ViewOnline Version of Record before inclusion in an issuee202217339 RelatedInformation