TY - JOUR
T1 - Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition
AU - Taleb, Mohammad
AU - Atabakhshi-Kashi, Mona
AU - Wang, Yazhou
AU - Rezvani Alanagh, Hamideh
AU - Farhadi Sabet, Zeinab
AU - Li, Fenfen
AU - Cheng, Keman
AU - Li, Chen
AU - Qi, Yingqiu
AU - Nie, Guangjun
AU - Ying, Zhao
N1 - Funding Information:
This work was supported by the Excellent Young Scientists Fund (31722021), the National Key R&D Program of China (2018YFA0208900), the National Natural Science Foundation of China (21877023, 51673051, and 51861145302), the Beijing Nova Program (Z171100001117010), the Beijing Nova Programme Interdisciplinary Cooperation Project (Z191100001119007), the Youth Innovation Promotion Association CAS (2017056), and the Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, CAS (NSKF202011). The authors are grateful for support of the CAS‐TWAS President's Fellowship for International Ph.D. Students.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.
PY - 2021/6/23
Y1 - 2021/6/23
N2 - The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (DPPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. DPPA is an inhibitory peptide of the PD-1/PD-L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.
AB - The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (DPPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. DPPA is an inhibitory peptide of the PD-1/PD-L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.
KW - combination therapy
KW - immune checkpoint inhibitors
KW - peptide amphiphile
KW - peptide nanoparticles
KW - vessel normalization
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U2 - 10.1002/adhm.202100051
DO - 10.1002/adhm.202100051
M3 - Article
C2 - 34021735
AN - SCOPUS:85106240640
VL - 10
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
SN - 2192-2640
IS - 12
M1 - 2100051
ER -