Engineered Bacterial Outer Membrane Vesicles as Controllable Two-Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy

Qingqing Feng, Xiaotu Ma, Keman Cheng, Guangna Liu, Yao Li, Yale Yue, Jie Liang, Lizhuo Zhang, Tianjiao Zhang, Xinwei Wang, Xiaoyu Gao, Guangjun Nie, Xiao Zhao

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The most immune cells infiltrating tumor microenvironment (TME), tumor-associated macrophages (TAMs) closely resemble immunosuppressive M2-polarized macrophages. Moreover, tumor cells exhibit high expression of CD47 “don't eat me” signal, which obstructs macrophage phagocytosis. The precise and efficient activation of TAMs is a promising approach to tumor immunotherapy; however, re-education of macrophages remains a challenge. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate macrophages. Here, an OMV-based controllable two-way adaptor is reported, in which a CD47 nanobody (CD47nb) is fused onto OMV surface (OMV-CD47nb), with the outer surface coated with a polyethylene glycol (PEG) layer containing diselenide bonds (PEG/Se) to form PEG/Se@OMV-CD47nb. The PEG/Se layer modification not only mitigates the immunogenicity of OMV-CD47nb, thereby remarkedly increasing the dose that can be administered safely through intravenous injection, but also equips the formulation with radiation-triggered controlled release of OMV-CD47nb. Application of radiation to tumors in mice injected with the nanoformulation results in remodeling of TME. As two-way adaptors, OMV-CD47nb activates TAM phagocytosis of tumor cells via multiple pathways, including induction of M1 polarization and blockade of “don't eat me” signal. Moreover, this activation of TAMs results in the stimulation of T cell-mediated antitumor immunity through effective antigen presentation.

Original languageEnglish (US)
Article number2206200
JournalAdvanced Materials
Volume34
Issue number40
DOIs
StatePublished - Oct 6 2022

Keywords

  • CD47
  • M1 polarization
  • outer membrane vesicles
  • tumor-associated macrophages
  • two-way adaptor

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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