iRGD Modified Chemo‐immunotherapeutic Nanoparticles for Enhanced Immunotherapy against Glioblastoma

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) a...

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Bibliographic Details
Published in:Advanced functional materials 2018-04, Vol.28 (17), p.n/a
Main Authors: Kuang, Jing, Song, Wen, Yin, Jun, Zeng, Xuan, Han, Song, Zhao, Yi‐Peng, Tao, Jun, Liu, Chuan‐Jun, He, Xiao‐Hua, Zhang, Xian‐Zheng
Format: Article
Language:English
Subjects:
Accumulation
Adults
Brain
Brain cancer
chemo‐immunotherapy
Cytokines
cytotoxic CD8+ T lymphocytes
Doxorubicin
glioblastoma
immune checkpoint inhibitors
Immunity
Lymphocytes
Materials science
Nanoparticles
Proteins
Side effects
Silicon dioxide
STING
Tumors
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Summary: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. Anti‐glioblastoma immunotherapy triggered by chemo‐immunotherapeutic nanoparticles:iRGD modified nanoparticles delivers immune checkpoint inhibitor and chemotherapeutic drugs into orthotopic glioma area. With the release of loaded drugs, tumor infiltrating lymphocytes are recruited and activated. The combinational chemo‐immunotherapeutic nanoparticles elicit significant antitumor immunity against glioblastoma.
ISSN:1616-301X
1616-3028
DOI:10.1002/adfm.201800025