Engineered Bacterial Outer Membrane Vesicles as Controllable Two‐Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy. Issue 40 (4th September 2022)

• Record Type: Journal Article
• Authors: Feng, Qingqing; Ma, Xiaotu; Cheng, Keman; Liu, Guangna; Li, Yao; Yue, Yale; Liang, Jie; Zhang, Lizhuo; Zhang, Tianjiao; Wang, Xinwei; Gao, Xiaoyu; Nie, Guangjun; Zhao, Xiao
• Is Part Of: Advanced materials. Volume 34:Issue 40(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-04
• Subjects: CD47 -- M1 polarization -- outer membrane vesicles -- tumor‐associated macrophages -- two‐way adaptor; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202206200
• Languages: English
• ISSNs: 0935-9648

Abstract

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. Abstract : An outer membrane vesicle (OMV)‐based controllable PEG/Se@OMV‐CD47nb remarkedly increase the dose that can be administered safely through intravenous injection. As two‐way adaptors, OMV‐CD47nb activate tumor‐associated macrophage (TAM) phagocytosis of tumor cells via inducing M1 polarization and blocking "don't eat me" signal. Moreover, this activation of TAMs results in the stimulation of T cell‐mediated antitumor immunity through effective antigen presentation.