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Tytuł pozycji:

A Novel Strategy Conjugating PD-L1 Polypeptide With Doxorubicin Alleviates Chemotherapeutic Resistance and Enhances Immune Response in Colon Cancer.

Tytuł:
A Novel Strategy Conjugating PD-L1 Polypeptide With Doxorubicin Alleviates Chemotherapeutic Resistance and Enhances Immune Response in Colon Cancer.
Autorzy:
Wang M; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.; College of Pharmacy, Shenzhen Technology University, Shenzhen, China.
Shu XS; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Li M; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Zhang Y; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Yao Y; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Huang X; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Li J; Department of Pathogen Biology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Wei P; Shenzhen University General Hospital, Department of Endocrinology, Shenzhen, China.
He Z; College of Pharmacy, Shenzhen Technology University, Shenzhen, China.
Lu J; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.; Institute of Integrated Bioinfomedicine & Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China.
Ying Y; Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
Źródło:
Frontiers in oncology [Front Oncol] 2021 Nov 10; Vol. 11, pp. 737323. Date of Electronic Publication: 2021 Nov 10 (Print Publication: 2021).
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: [Lausanne : Frontiers Research Foundation]
References:
Chem Biol. 2010 May 28;17(5):421-33. (PMID: 20534341)
Trends Biotechnol. 2010 Oct;28(10):517-25. (PMID: 20719399)
Nature. 2001 Apr 26;410(6832):1107-11. (PMID: 11323675)
Life Sci. 2018 May 1;200:26-30. (PMID: 29534993)
Lancet Oncol. 2015 Feb;16(2):200-7. (PMID: 25589192)
Biochemistry. 1990 Mar 13;29(10):2538-49. (PMID: 2334681)
J Clin Invest. 2015 Sep;125(9):3384-91. (PMID: 26325035)
Curr Top Med Chem. 2015;15(12):1082-101. (PMID: 25866267)
Sci Transl Med. 2016 Mar 2;8(328):328rv4. (PMID: 26936508)
Pharmacol Res. 2019 Aug;146:104276. (PMID: 31112750)
Cancer Cell. 2015 Apr 13;27(4):450-61. (PMID: 25858804)
Theranostics. 2015 Jan 01;5(1):23-42. (PMID: 25553096)
Exp Ther Med. 2018 Apr;15(4):3751-3758. (PMID: 29581735)
Chem Biol Drug Des. 2013 Jan;81(1):113-21. (PMID: 23253133)
Molecules. 2019 Mar 07;24(5):. (PMID: 30866536)
J Nucl Med. 2010 Aug;51(8):1167-70. (PMID: 20660380)
DNA Repair (Amst). 2014 Dec;24:15-25. (PMID: 25460919)
J Cancer Res Ther. 2014 Oct-Dec;10(4):853-8. (PMID: 25579518)
J Cell Physiol. 2019 Aug;234(10):16824-16837. (PMID: 30784085)
Clin Colorectal Cancer. 2015 Mar;14(1):1-10. (PMID: 25579803)
N Engl J Med. 2016 Nov 10;375(19):1823-1833. (PMID: 27718847)
Biomaterials. 2018 Nov;182:216-226. (PMID: 30138784)
Cancer Immunol Res. 2014 Apr;2(4):361-70. (PMID: 24764583)
Mol Pharmacol. 1994 Apr;45(4):649-56. (PMID: 8183243)
Trends Immunol. 2015 Apr;36(4):265-76. (PMID: 25797516)
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3011-6. (PMID: 18287011)
Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8486-8493. (PMID: 32234785)
Curr Opin Chem Biol. 2010 Aug;14(4):529-37. (PMID: 20643572)
Angew Chem Int Ed Engl. 2015 Sep 28;54(40):11760-4. (PMID: 26259671)
Nature. 2014 Nov 27;515(7528):558-62. (PMID: 25428503)
J Enzyme Inhib Med Chem. 2018 Dec;33(1):890-904. (PMID: 29723068)
Annu Rev Med. 2013;64:15-29. (PMID: 23043493)
Cancer Treat Rev. 2012 Nov;38(7):926-34. (PMID: 22658913)
Curr Opin Immunol. 2012 Apr;24(2):207-12. (PMID: 22236695)
Nat Commun. 2017 Nov 9;8(1):1390. (PMID: 29123088)
Contributed Indexing:
Keywords: PD-L1 targeting polypeptide; chemotherapeutics drug release; colon cancer; pH sensitive linker; target delivery system
Entry Date(s):
Date Created: 20211203 Latest Revision: 20220428
Update Code:
20240105
PubMed Central ID:
PMC8631515
DOI:
10.3389/fonc.2021.737323
PMID:
34858817
Czasopismo naukowe
Background: Modifying the structure of anti-tumor chemotherapy drug is of significance to enhance the specificity and efficacy of drug-delivery. A novel proteolysis resistant PD-L1-targeted peptide (PPA1) has been reported to bind to PD-L1 and disrupt the PD-1/PD-L1 interaction, thus appearing as an outstanding tumor-targeting modification of synergistic drug conjugate for effective anti-tumor treatment. However, the combination regimen of coupling PD-L1 polypeptide with chemotherapeutic drug in tumoricidal treatment has not been reported thus far.
Methods: We developed a novel synergistic strategy by conjugating PPA1 to doxorubicin (DOX) with a pH sensitive linker that can trigger the release of DOX near acidic tumor tissues. The binding affinity of PPA1-DOX with PD-L1 and the acid-sensitive cleavage of PPA1-DOX were investigated. A mouse xenograft model of colon cancer was used to evaluate the biodistribution, cytotoxicity and anti-tumor activity of PPA1-DOX.
Results: PPA1-DOX construct showed high binding affinity with PD-L1 in vitro and specifically enriched within tumor when administered in vivo . PPA1-DOX exhibited a significantly lower toxicity and a remarkably higher antitumor activity in vivo , as compared with free PPA1, random polypeptide-DOX conjugate, DOX, or 5-FU, respectively. Moreover, increased infiltration of both CD4 + and CD8 + T cells was found in tumors from PPA1-DOX treated mice.
Conclusions: We describe here for the first time that the dual-functional conjugate PPA1-DOX, which consist of the PD-L1-targeted polypeptide that renders both the tumor-specific drug delivery and inhibitory PD-1/PD-L1 immune checkpoint inhibition, and a cytotoxic agent that is released and kills tumor cells once reaching tumor tissues, thus representing a promising therapeutic option for colon cancer with improved efficacy and reduced toxicity.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Wang, Shu, Li, Zhang, Yao, Huang, Li, Wei, He, Lu and Ying.)

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