PMID- 36427459
OWN - NLM
STAT- MEDLINE
DCOM- 20230213
LR  - 20230213
IS  - 1521-4095 (Electronic)
IS  - 0935-9648 (Linking)
VI  - 35
IP  - 6
DP  - 2023 Feb
TI  - Checkpoint Nano-PROTACs for Activatable Cancer Photo-Immunotherapy.
PG  - e2208553
LID - 10.1002/adma.202208553 [doi]
AB  - 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/SIRPalpha 
      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.
CI  - (c) 2022 Wiley-VCH GmbH.
FAU - Zhang, Chi
AU  - Zhang C
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
FAU - Xu, Mengke
AU  - Xu M
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
FAU - He, Shasha
AU  - He S
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
FAU - Huang, Jingsheng
AU  - Huang J
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
FAU - Xu, Cheng
AU  - Xu C
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
FAU - Pu, Kanyi
AU  - Pu K
AUID- ORCID: 0000-0002-8064-6009
AD  - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang 
      Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
AD  - Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang 
      Drive, Singapore, 636921, Singapore.
LA  - eng
GR  - 2019-T1-002-045/Academic Research Fund Tier 1/
GR  - RG125/19/Academic Research Fund Tier 1/
GR  - MOE2018-T2-2-042/Academic Research Fund Tier 2/
GR  - SERC A18A8b0059/A*STAR SERC AME Programmatic Fund/
PT  - Journal Article
DEP - 20221218
PL  - Germany
TA  - Adv Mater
JT  - Advanced materials (Deerfield Beach, Fla.)
JID - 9885358
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Humans
MH  - Caspase 3
MH  - *Immunotherapy
MH  - *Neoplasms/drug therapy
MH  - Macrophages/metabolism
MH  - Immunosuppressive Agents/therapeutic use
OTO - NOTNLM
OT  - PROTAC
OT  - cancer immunotherapy
OT  - checkpoint blockade
OT  - phototherapy
EDAT- 2022/11/26 06:00
MHDA- 2023/02/14 06:00
CRDT- 2022/11/25 18:24
PHST- 2022/11/04 00:00 [revised]
PHST- 2022/09/17 00:00 [received]
PHST- 2022/11/26 06:00 [pubmed]
PHST- 2023/02/14 06:00 [medline]
PHST- 2022/11/25 18:24 [entrez]
AID - 10.1002/adma.202208553 [doi]
PST - ppublish
SO  - Adv Mater. 2023 Feb;35(6):e2208553. doi: 10.1002/adma.202208553. Epub 2022 Dec 
      18.