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Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor

Cancer metastases is still a hurdle for good prognosis and live quality of breast cancer patients. Treatment strategies that can inhibit metastatic cancer while treating primary cancer are needed to improve the therapeutic effect of breast cancer. Methods: In this study, a dual functional drug conju...

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Autores principales: Huang, Zeqian, Wei, Gaofei, Zeng, Zishan, Huang, Yanjuan, Huang, Liangfeng, Shen, Yifeng, Sun, Xiaoqi, Xu, Congjun, Zhao, Chunshun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735384/
https://www.ncbi.nlm.nih.gov/pubmed/31534502
http://dx.doi.org/10.7150/thno.35343
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author Huang, Zeqian
Wei, Gaofei
Zeng, Zishan
Huang, Yanjuan
Huang, Liangfeng
Shen, Yifeng
Sun, Xiaoqi
Xu, Congjun
Zhao, Chunshun
author_facet Huang, Zeqian
Wei, Gaofei
Zeng, Zishan
Huang, Yanjuan
Huang, Liangfeng
Shen, Yifeng
Sun, Xiaoqi
Xu, Congjun
Zhao, Chunshun
author_sort Huang, Zeqian
collection PubMed
description Cancer metastases is still a hurdle for good prognosis and live quality of breast cancer patients. Treatment strategies that can inhibit metastatic cancer while treating primary cancer are needed to improve the therapeutic effect of breast cancer. Methods: In this study, a dual functional drug conjugate comprised of protoporphyrin IX and NLG919, a potent indoleamine-2,3-dioxygenase (IDO) inhibitor, is designed to combine photodynamic therapy and immune checkpoint blockade to achieve both primary tumor and distant metastases inhibition. Liposomal delivery is applied to improve the biocompatibility and tumor accumulation of the drug conjugate (PpIX-NLG@Lipo). A series of in vitro and in vivo experiments were carried out to examine the PDT effect and IDO inhibition activity of PpIX-NLG@Lipo, and subsequently evaluate its anti-tumor capability in the bilateral 4T1 tumor-bearing mice. Results: The in vitro and in vivo experiments demonstrated that PpIX-NLG@Lipo possess strong ability of ROS generation to damage cancer cells directly through PDT. Meanwhile, PpIX-NLG@ Lipo can induce immunogenic cell death to elicit the host immune system. Furthermore, PpIX-NLG@Lipo interferes the activity of IDO, which can amplify PDT-induced immune responses, leading to an increasing amount of CD8(+) T lymphocytes infiltrated into tumor site, finally achieve both primary and distant tumor inhibition. Conclusion: This work presents a novel conjugate approach to synergize photodynamic therapy and IDO blockade for enhanced cancer therapy through simultaneously inhibiting both primary and distant metastatic tumor.
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spelling pubmed-67353842019-09-18 Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor Huang, Zeqian Wei, Gaofei Zeng, Zishan Huang, Yanjuan Huang, Liangfeng Shen, Yifeng Sun, Xiaoqi Xu, Congjun Zhao, Chunshun Theranostics Research Paper Cancer metastases is still a hurdle for good prognosis and live quality of breast cancer patients. Treatment strategies that can inhibit metastatic cancer while treating primary cancer are needed to improve the therapeutic effect of breast cancer. Methods: In this study, a dual functional drug conjugate comprised of protoporphyrin IX and NLG919, a potent indoleamine-2,3-dioxygenase (IDO) inhibitor, is designed to combine photodynamic therapy and immune checkpoint blockade to achieve both primary tumor and distant metastases inhibition. Liposomal delivery is applied to improve the biocompatibility and tumor accumulation of the drug conjugate (PpIX-NLG@Lipo). A series of in vitro and in vivo experiments were carried out to examine the PDT effect and IDO inhibition activity of PpIX-NLG@Lipo, and subsequently evaluate its anti-tumor capability in the bilateral 4T1 tumor-bearing mice. Results: The in vitro and in vivo experiments demonstrated that PpIX-NLG@Lipo possess strong ability of ROS generation to damage cancer cells directly through PDT. Meanwhile, PpIX-NLG@ Lipo can induce immunogenic cell death to elicit the host immune system. Furthermore, PpIX-NLG@Lipo interferes the activity of IDO, which can amplify PDT-induced immune responses, leading to an increasing amount of CD8(+) T lymphocytes infiltrated into tumor site, finally achieve both primary and distant tumor inhibition. Conclusion: This work presents a novel conjugate approach to synergize photodynamic therapy and IDO blockade for enhanced cancer therapy through simultaneously inhibiting both primary and distant metastatic tumor. Ivyspring International Publisher 2019-07-29 /pmc/articles/PMC6735384/ /pubmed/31534502 http://dx.doi.org/10.7150/thno.35343 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Huang, Zeqian
Wei, Gaofei
Zeng, Zishan
Huang, Yanjuan
Huang, Liangfeng
Shen, Yifeng
Sun, Xiaoqi
Xu, Congjun
Zhao, Chunshun
Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title_full Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title_fullStr Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title_full_unstemmed Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title_short Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor
title_sort enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and ido inhibitor
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735384/
https://www.ncbi.nlm.nih.gov/pubmed/31534502
http://dx.doi.org/10.7150/thno.35343
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