Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/164392
Title: Checkpoint nano-PROTACs for activatable cancer photo-immunotherapy
Authors: Zhang, Chi
Xu, Mengke
He, Shasha
Huang, Jingsheng
Xu, Cheng
Pu, Kanyi
Keywords: Science::Chemistry
Issue Date: 2022
Source: Zhang, C., Xu, M., He, S., Huang, J., Xu, C. & Pu, K. (2022). Checkpoint nano-PROTACs for activatable cancer photo-immunotherapy. Advanced Materials. https://dx.doi.org/10.1002/adma.202208553
Project: 2019-T1-002-045 
RG125/19 
MOE2018-T2-2-042 
SERC A18A8b0059 
Journal: Advanced Materials 
Abstract: Checkpoint immunotherapy holds great potential to treat malignancies via blocking the immunosuppressive signaling pathways, which however suffers from inefficiency and off-target adverse effects. Herein, checkpoint nano-proteolysis targeting chimeras (nano-PROTACs) in combination with photodynamic tumor regression and immunosuppressive protein degradation to block checkpoint signaling pathways for activatable cancer photo-immunotherapy are reported. These nano-PROTACs are composed of a photosensitizer (protoporphyrin IX, PpIX) and an Src homology 2 domain-containing phosphatase 2 (SHP2)-targeting PROTAC peptide (aPRO) via a caspase 3-cleavable segment. aPRO is activated by the increased expression of caspase 3 in tumor cells after phototherapeutic treatment and induces targeted degradation of SHP2 via the ubiquitin-proteasome system. The persistent depletion of SHP2 blocks the immunosuppressive checkpoint signaling pathways (CD47/SIRPα and PD-1/PD-L1), thus reinvigorating antitumor macrophages and T cells. Such a checkpoint PROTAC strategy synergizes immunogenic phototherapy to boost antitumor immune response. Thus, this study represents a generalized PROTAC platform to modulate immune-related signaling pathways for improved anticancer therapy.
URI: https://hdl.handle.net/10356/164392
ISSN: 0935-9648
DOI: 10.1002/adma.202208553
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
School of Chemistry, Chemical Engineering and Biotechnology 
Rights: © 2022 Wiley-VCH GmbH. All rights reserved. This is the peer reviewed version of the following article: Zhang, C., Xu, M., He, S., Huang, J., Xu, C. & Pu, K. (2022). Checkpoint nano-PROTACs for activatable cancer photo-immunotherapy. Advanced Materials, which has been published in final form at https://doi.org/10.1002/adma.202208553. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:CCEB Journal Articles
LKCMedicine Journal Articles

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