Hybrid Nanoreactors: Enabling an Off‐the‐Shelf Strategy for Concurrently Enhanced Chemo‐immunotherapy

Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death a...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-09, Vol.57 (36), p.11764-11769
Main Authors: Yang, Yannan, Tang, Jie, Abbaraju, Prasanna Lakshmi, Jambhrunkar, Manasi, Song, Hao, Zhang, Min, Lei, Chang, Fu, Jianye, Gu, Zhengying, Liu, Yang, Yu, Chengzhong
Format: Article
Language:English
Subjects:
Antigen (tumor-associated)
Antigens
Cancer
Cancer immunotherapy
Catalysts
Cell death
chemoimmunotherapy
Glutathione
Immune checkpoint
immune checkpoint blockades
Immune system
immunogenic cell death
Immunogenicity
Immunosuppression
immunosuppressive tumors
Immunotherapy
nanoreactors
Nanotechnology
T cell receptors
Tumors
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Summary:Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo‐immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off‐the‐shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation. A hybrid nanoreactor based on dendritic mesoporous silica nanoparticles containing copper and tetrasulfide that can trigger Fenton's reaction and glutathione depletion has been developed for simultaneously amplifying immunogenic cell death and activating the immune system. It exhibits excellent synergism with immune checkpoint blockades for treating immunosuppressive tumors by concurrently enhanced chemo/immunotherapy.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201807595