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  2. Multifunctional Nanodrug Mediates Synergistic Photodynamic Therapy and MDSCs-Targeting Immunotherapy of Colon Cancer

Multifunctional Nanodrug Mediates Synergistic Photodynamic Therapy and MDSCs-Targeting Immunotherapy of Colon Cancer

  • Adv Sci (Weinh). 2021 Jul;8(14):e2100712. doi: 10.1002/advs.202100712.
Dongbing Ding 1 Huihai Zhong 2 Rongpu Liang 1 Tianyun Lan 3 Xudong Zhu 1 Shengxin Huang 1 Yong Wang 4 Jun Shao 1 Xintao Shuai 1 2 Bo Wei 1
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
  • 2 PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510275, China.
  • 3 Central Laboratory, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
  • 4 College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China.
Abstract

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.

Keywords

PI3Kγ inhibitor; immunotherapy; multifunctional nanodrug; myeloid-derived suppressive cells (MDSCs); photodynamic therapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100716
    99.69%, PI3Kγ抑制剂