Multifunctional Nanodrug Mediates Synergistic Photodynamic Therapy and MDSCs-Targeting Immunotherapy of Colon Cancer
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH..
An ideal tumor treatment is supposed to eliminate the primary tumor and simultaneously trigger the host antitumor immune responses to prevent tumor recurrence and metastasis. Herein, a liposome encapsulating phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor IPI-549 and photosensitizer chlorin e6 (Ce6), denoted by LIC, is prepared for colon cancer treatment. LIC internalized into CT26 cells generates reactive oxygen species (ROS) under laser irradiation to cause immunogenic tumor cell death, during which immunostimulatory signals such as calreticulin are released to further induce T lymphocyte-mediated tumor cell killing. Meanwhile, IPI-549 transported by liposome can inhibit PI3Kγ in the myeloid-derived suppressive cells (MDSCs), resulting in downregulation of arginase 1 (Arg-1) and ROS to promote MDSCs apoptosis and reduce their immunosuppressive activity to CD8+ T cells. LIC-mediated immunogenic photodynamic therapy synergizes with MDSCs-targeting immunotherapy, which significantly inhibits tumor growth via facilitating the dendritic cell maturation and tumor infiltration of CD8+ T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2-like tumor-associated macrophages. Moreover, the synergistic therapy increases the number of effector memory T cells (TEM ) in spleen, which suggests a favorable immune memory to prevent tumor recurrence and metastasis. The Ce6 and IPI-549-coloaded multifunctional nanodrug demonstrates high efficacy in colon cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 8(2021), 14 vom: 15. Juli, Seite e2100712 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ding, Dongbing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.12.2021 Date Revised 14.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202100712 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325710570 |
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| 520 | |a An ideal tumor treatment is supposed to eliminate the primary tumor and simultaneously trigger the host antitumor immune responses to prevent tumor recurrence and metastasis. Herein, a liposome encapsulating phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor IPI-549 and photosensitizer chlorin e6 (Ce6), denoted by LIC, is prepared for colon cancer treatment. LIC internalized into CT26 cells generates reactive oxygen species (ROS) under laser irradiation to cause immunogenic tumor cell death, during which immunostimulatory signals such as calreticulin are released to further induce T lymphocyte-mediated tumor cell killing. Meanwhile, IPI-549 transported by liposome can inhibit PI3Kγ in the myeloid-derived suppressive cells (MDSCs), resulting in downregulation of arginase 1 (Arg-1) and ROS to promote MDSCs apoptosis and reduce their immunosuppressive activity to CD8+ T cells. LIC-mediated immunogenic photodynamic therapy synergizes with MDSCs-targeting immunotherapy, which significantly inhibits tumor growth via facilitating the dendritic cell maturation and tumor infiltration of CD8+ T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2-like tumor-associated macrophages. Moreover, the synergistic therapy increases the number of effector memory T cells (TEM ) in spleen, which suggests a favorable immune memory to prevent tumor recurrence and metastasis. The Ce6 and IPI-549-coloaded multifunctional nanodrug demonstrates high efficacy in colon cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a PI3Kγ inhibitor | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a multifunctional nanodrug | |
| 650 | 4 | |a myeloid-derived suppressive cells (MDSCs) | |
| 650 | 4 | |a photodynamic therapy | |
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| 700 | 1 | |a Zhong, Huihai |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Rongpu |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Tianyun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Shengxin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Xintao |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Bo |e verfasserin |4 aut | |
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