Biodegradable Poly(γ-glutamic acid)@glucose oxidase@carbon dot nanoparticles for simultaneous multimodal imaging and synergetic cancer therapy

Ming Zhang*, Wentao Wang, Fan Wu, Tao Zheng, Jon Ashley, Mohsen Mohammadniaei, Qicheng Zhang, Mingqian Wang, Li Li, Jian Shen*, Yi Sun*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

It is known that tumor antigens could induce obvious anti-tumor immune responses for efficient cancer immunotherapy when combined with checkpoint blockade. However, the amount of tumor antigens is often limited due to the suppressive tumor microenvironment (TME). Here, a new type of nanomaterial was developed to improve tumor treatment by the combined action of starving therapy/photodynamic therapy (PDT)/photothermal therapy (PTT) and checkpoint-blockade immunotherapy. In detail, the immunoadjuvant nanoagents (γ-PGA@GOx@Mn,Cu-CDs) were fabricated by integrating the gamma-glutamyl transferase (GGT) enzyme-induced cellular uptake polymer-poly (γ-glutamic acid) (γ-PGA), a glucose-metabolic reaction agent - glucose oxidase (GOx), Mn,Cu-doped carbon dots (CDs) as photosensitizer and self-supplied oxygenator nanodots. γ-PGA@GOx@Mn,Cu-CDs nanoparticles (NPs) showed long retention time at the tumor acidic microenvironment and could further target cancer cells. The NPs also displayed both photothermal and photodynamic effects under laser irradiation at 730 nm. Interestingly, the endogenous generation of hydrogen peroxide (H2O2) caused by the nanoreactors could significantly relieve tumor hypoxia and further enhance in vivo PDT. By synergistically combining the NPs-based starving-like therapy/PDT/PTT and check-point-blockade therapy, the treatment efficiency was significantly improved. More importantly, the systematic antitumor immune response would eliminate non-irradiated tumors as well, which is promising for metastasis inhibition.
Original languageEnglish
Article number120106
JournalBiomaterials
Volume252
Number of pages12
ISSN0142-9612
DOIs
Publication statusPublished - 2020

Keywords

  • Tumor microenvironment
  • Checkpoint-blockade immunotherapy
  • Singlet oxygen
  • Hyperthermia
  • Metastasis inhibition

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