TY - JOUR
T1 - Engineered Bacterial Outer Membrane Vesicles as Controllable Two-Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy
AU - Feng, Qingqing
AU - Ma, Xiaotu
AU - Cheng, Keman
AU - Liu, Guangna
AU - Li, Yao
AU - Yue, Yale
AU - Liang, Jie
AU - Zhang, Lizhuo
AU - Zhang, Tianjiao
AU - Wang, Xinwei
AU - Gao, Xiaoyu
AU - Nie, Guangjun
AU - Zhao, Xiao
N1 - Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/10/6
Y1 - 2022/10/6
N2 - 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.
AB - 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.
KW - CD47
KW - M1 polarization
KW - outer membrane vesicles
KW - tumor-associated macrophages
KW - two-way adaptor
UR - http://www.scopus.com/inward/record.url?scp=85137347986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137347986&partnerID=8YFLogxK
U2 - 10.1002/adma.202206200
DO - 10.1002/adma.202206200
M3 - Article
C2 - 35985666
AN - SCOPUS:85137347986
SN - 0935-9648
VL - 34
JO - Advanced Materials
JF - Advanced Materials
IS - 40
M1 - 2206200
ER -