PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy.

Autor:	Xiao Z; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China., Wang D; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China., Wang C; CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, PR China., Chen Z; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China., Huang C; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China., Yang Y; CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, PR China., Xie L; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Zhang L; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Xu L; CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, PR China., Zhang MR; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Hu K; CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, PR China.; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan., Li Z; CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, PR China.; School of Nanoscience and Technology Chinese Academy of Sciences, Beijing, 101400, PR China., Luo L; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China.
Jazyk:	angličtina
Zdroj:	Materials today. Bio [Mater Today Bio] 2022 May 18; Vol. 15, pp. 100297. Date of Electronic Publication: 2022 May 18 (Print Publication: 2022).
DOI:	10.1016/j.mtbio.2022.100297
Abstrakt:	Intratumoral immunotherapeutic hydrogel administration is emerging as an effective method for inducing a durable and robust antitumor immune response. However, scaffold hydrogels that can synergize with the loaded drugs, thus potentiating therapeutic efficacy, are limited. Here, we report a ternary hydrogel composed of polyvinyl alcohol (PVA), polyethylenimine (PEI)‒a cationic polymer with potential immunoactivation effects, and magnesium ions‒a stimulator of the adaptive immune response, which exhibits an intrinsic immunomodulation function of reversing the immunologically "cold" phenotype of a murine breast tumor to a "hot" phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel (PEIGel) encapsulating an immune checkpoint blockade (ICB) inhibitor‒anti-PD-L1 antibody (α-PDL1) exhibits synergistic effects resulting in elimination of primary tumors and remote metastases and prevention of tumor relapse after surgical resection. A preliminary mechanistic study revealed a probably hidden role of PEI in modulating the polyamine metabolism/catabolism of tumors to potentiate the immune adjuvant effect. These results deepen our understanding of the innate immune activation function of PEI and pave the way for harnessing PEI as an immune adjuvant for ICB therapy. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors.)
Databáze:	MEDLINE
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