In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma

It is well known that glioma is currently the most malignant brain tumor. Because of the existence of blood-brain barrier (BBB) and tumor cell heterogeneity, systemic chemotherapy exerts unsatisfied therapeutic effect for the treatment of glioma after surgical resection and may even damage the body&...

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Bibliographic Details
Published in:Journal of controlled release 2022-05, Vol.345, p.786-797
Main Authors: Wang, Xiaoqi, Ye, Lu, He, Weichong, Teng, Chuanhui, Sun, Shanbo, Lu, Hongdan, Li, Shengnan, Lv, Lingyan, Cao, Xiang, Yin, Haoyuan, Lv, Wei, Xin, Hongliang
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Antigens, Neoplasm - therapeutic use
Brain Neoplasms - drug therapy
Brain Neoplasms - pathology
Cell Line, Tumor
Chemo-immunotherapy
CpG
Delayed-Action Preparations - therapeutic use
Drug delivery
Drug Delivery Systems
Glioma
Glioma - drug therapy
Glioma - pathology
Humans
Hydrogels - therapeutic use
Immunologic Factors - therapeutic use
Immunotherapy
In situ hydrogel
Nanoparticles
Tumor Microenvironment
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Summary:It is well known that glioma is currently the most malignant brain tumor. Because of the existence of blood-brain barrier (BBB) and tumor cell heterogeneity, systemic chemotherapy exerts unsatisfied therapeutic effect for the treatment of glioma after surgical resection and may even damage the body's immune system. Here, we developed an in situ sustained-release hydrogel delivery system for combined chemo-immunotherapy of glioma by combined chemotherapy drug and immunoadjuvant through the resection cavity local delivery. Briefly, glioma homing peptide modified paclitaxel targeting nanoparticles (PNPPTX) and mannitolated immunoadjuvant CpG targeting nanoparticles (MNPCpG) were embedded into PLGA1750-PEG1500-PLGA1750 thermosensitive hydrogel framework (PNPPTX&MNPCpG@Gel). The in vitro and in vivo results showed that the targeting nanoparticles-hydrogel hybrid system could cross-link into a gel drug reservoir when injected into the resection cavity of glioma. And then, the sustained-release PNPPTX could target the residual infiltration glioma cells and produce tumor antigens. Meanwhile, MNPCpG targeted and activated the antigen-presenting cells, which enhanced the tumor antigen presentation ability and activated CD8+T and NK cells to reverse immunosuppression of glioma microenvironment. This study indicated that the PNPPTX&MNPCpG@Gel system could enhance the therapeutic effect of glioma by chemo-immunotherapy. [Display omitted] •Targeting nanoparticles-hydrogel hybrid system simultaneously delivers PTX and CpG for glioma recurrence inhibition.•The in suite hydrogel based local delivery system bypasses the BBB and reaches the target cells directly.•Targeting nanoparticles-hydrogel hybrid system efficiently reduces glioma recurrence within one dose of administration in the cavity of glioma resection.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2022.03.050