Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Ming Zhang, Xuefeng Jiang, Qicheng Zhang, Tao Zheng, Mohsen Mohammadniaei, Wentao Wang*, Jian Shen, Yi Sun

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.

Original languageEnglish
Article number2102274
JournalAdvanced Functional Materials
Volume31
Issue number38
Number of pages13
ISSN1616-301X
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This work was supported by the Villum Foundation of Denmark (Grant No. 13153). All animal experiment procedures were conducted by the guidelines approved and supervised by the Ethics Committee of Nanjing Normal University and Keygen Biotech. Co., Ltd.

Keywords

  • Cytotoxic T lymphocytes
  • Glioblastomas
  • Immunotherapy
  • Photodynamic therapy
  • Reactive oxygen species

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