Bioinspired Engineering of a Bacterium-Like Metal-Organic Framework for Cancer Immunotherapy

Po-Ming Chen, Wen-Yu Pan, Yang-Bao Miao, Yu-Miao Liu, Po-Kai Luo, Hieu Nghia Phung, Wen-Wei Wu, Yi-Hsin Ting, Ching-Yen Yeh, Min-Chun Chiang, Wei-Tso Chia, Hsing-Wen Sung

Research output: Contribution to journalArticlepeer-review

Abstract

Bacteria-mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium-like metal-organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side-effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2-aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium-like MOFs under exposure to an near-infrared laser and the immune checkpoint blockade of systemically administered alpha PD-1 is evaluated in tumor-bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis.

Original languageEnglish
Article number2003764
Number of pages12
JournalAdvanced Functional Materials
DOIs
StateE-pub ahead of print - 18 Aug 2020

Keywords

  • bacteria-mediated tumor therapy
  • checkpoint blockade
  • combination therapy
  • in situ vaccination
  • metal-organic framework
  • CHECKPOINT BLOCKADE
  • IMMUNE-RESPONSES
  • THERAPY
  • SIZE
  • ACTIVATION
  • ABLATION
  • SHAPE
  • PD-1

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