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iRGD Modified Chemo‐immunotherapeutic Nanoparticles for Enhanced Immunotherapy against Glioblastoma
Author(s) -
Kuang Jing,
Song Wen,
Yin Jun,
Zeng Xuan,
Han Song,
Zhao YiPeng,
Tao Jun,
Liu ChuanJun,
He XiaoHua,
Zhang XianZheng
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201800025
Subject(s) - glioma , cancer research , immunotherapy , cd8 , brain tumor , in vivo , doxorubicin , glioblastoma , downregulation and upregulation , cancer immunotherapy , immune system , materials science , medicine , biology , chemotherapy , immunology , pathology , biochemistry , microbiology and biotechnology , gene
Glioblastoma is the most common primary brain tumor in adults and still remains incurable, due to the limited accumulation of drugs in the tumor area. Herein, iRGD‐modified nanoparticles, DOX@MSN‐SS‐iRGD&1MT, are developed for simultaneous delivery of chemotherapeutic agents (doxorubicin, DOX) and immune checkpoint inhibitor (1‐methyltryptophan, 1MT) into orthotopic glioma. The nanoparticles are comprised of mesoporous silica nanoparticles loaded with DOX, combined with Asp‐Glu‐Val‐Asp (DEVD) connected 1MT, and finally modified by iRGD. These nanoparticles show the capability of penetrating through blood brain barrier into the tumor area, and significantly improve accumulation of drugs in orthotopic brain tumors with minimal side effects. The nanoparticles also activate cytotoxic CD8 + T lymphocytes and inhibit CD4 + T cells in both GL261 cells cocultured with splenocytes in vitro and GL261‐luc orthotopic tumors in vivo. Moreover, the expression of antitumor cytokines IFNα/β, IFN‐γ, TNF, IL‐17, STING, and GrzB is upregulated while protumor proteins p‐STAT3 and IL‐10 are downregulated in the brain tumor area. This study demonstrates the advantages of chemo‐immunotherapeutic nanoparticles accumulated in the brain tumor area and their effectively inhibiting tumor proliferation, which establishes a delivery platform to promote antitumor immunity against glioblastoma.