Self-Delivery Photo-Immune Stimulators for Photodynamic Sensitized Tumor Immunotherapy
Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-fre...
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| Published in | ACS nano Vol. 14; no. 12; pp. 17100 - 17113 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
American Chemical Society
22.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1936-0851 1936-086X 1936-086X |
| DOI | 10.1021/acsnano.0c06765 |
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| Abstract | Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy. |
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| AbstractList | Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy.Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy. Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy. |
| Author | Li, Shi-Ying Huang, Chu-Yu Cheng, Hong Liu, Yi-Bin Chen, Xia-Yun Zheng, Rong-Rong Zhao, Lin-Ping Deng, Fu-An Yu, Xi-Yong Huang, Jia-Qi |
| AuthorAffiliation | Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering |
| AuthorAffiliation_xml | – name: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – name: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering |
| Author_xml | – sequence: 1 givenname: Lin-Ping surname: Zhao fullname: Zhao, Lin-Ping organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 2 givenname: Rong-Rong surname: Zheng fullname: Zheng, Rong-Rong organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 3 givenname: Jia-Qi surname: Huang fullname: Huang, Jia-Qi organization: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering – sequence: 4 givenname: Xia-Yun surname: Chen fullname: Chen, Xia-Yun organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 5 givenname: Fu-An surname: Deng fullname: Deng, Fu-An organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 6 givenname: Yi-Bin surname: Liu fullname: Liu, Yi-Bin organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 7 givenname: Chu-Yu surname: Huang fullname: Huang, Chu-Yu organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 8 givenname: Xi-Yong surname: Yu fullname: Yu, Xi-Yong email: yuxycn@aliyun.com organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital – sequence: 9 givenname: Hong orcidid: 0000-0002-3560-4432 surname: Cheng fullname: Cheng, Hong email: chengh@smu.edu.cn organization: Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering – sequence: 10 givenname: Shi-Ying orcidid: 0000-0003-0666-7634 surname: Li fullname: Li, Shi-Ying email: lisy-sci@gzhmu.edu.cn organization: Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital |
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