Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma.
hepatocellular carcinoma
interfering peptides
tumor-penetrating peptides
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
06 Oct 2021
06 Oct 2021
Historique:
received:
06
09
2021
revised:
29
09
2021
accepted:
30
09
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
24
10
2021
Statut:
epublish
Résumé
The interfering peptides that block protein-protein interactions have been receiving increasing attention as potential therapeutic tools. We measured the internalization and biological effect of four bi-functional tumor-penetrating and interfering peptides into primary hepatocytes isolated from three non-malignant and 11 hepatocellular carcinomas. These peptides are internalized in malignant hepatocytes but not in non-malignant cells. Furthermore, the degree of peptide internalization correlated with receptor expression level and tumor aggressiveness levels. Importantly, penetration of the peptides iRGD-IP, LinTT1-IP, TT1-IP, and RPARPAR-IP induced apoptosis of the malignant hepatocytes without effect on non-malignant cells. Receptor expression levels correlated with the level of peptide internalization and aggressiveness of the tumor. This study highlights the potential to exploit the expression of tumor-penetrating peptide receptors as a predictive marker of liver tumor aggressiveness. These bi-functional peptides could be developed for personalized tumor treatment.
Sections du résumé
BACKGROUND
BACKGROUND
The interfering peptides that block protein-protein interactions have been receiving increasing attention as potential therapeutic tools.
METHODS
METHODS
We measured the internalization and biological effect of four bi-functional tumor-penetrating and interfering peptides into primary hepatocytes isolated from three non-malignant and 11 hepatocellular carcinomas.
RESULTS
RESULTS
These peptides are internalized in malignant hepatocytes but not in non-malignant cells. Furthermore, the degree of peptide internalization correlated with receptor expression level and tumor aggressiveness levels. Importantly, penetration of the peptides iRGD-IP, LinTT1-IP, TT1-IP, and RPARPAR-IP induced apoptosis of the malignant hepatocytes without effect on non-malignant cells.
CONCLUSION
CONCLUSIONS
Receptor expression levels correlated with the level of peptide internalization and aggressiveness of the tumor. This study highlights the potential to exploit the expression of tumor-penetrating peptide receptors as a predictive marker of liver tumor aggressiveness. These bi-functional peptides could be developed for personalized tumor treatment.
Identifiants
pubmed: 34683924
pii: pharmaceutics13101631
doi: 10.3390/pharmaceutics13101631
pmc: PMC8541685
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Inserm
ID : 2018
Organisme : European Regional Development Fund
ID : 2014-2020.4.01.15-0012
Organisme : Estonian Research Council
ID : PRG230 and EAG79
Références
Ann Surg Oncol. 2009 Sep;16(9):2539-46
pubmed: 19533247
FASEB J. 2000 Dec;14(15):2532-9
pubmed: 11099472
Gastroenterology. 2012 Oct;143(4):986-94.e3; quiz e14-5
pubmed: 22750200
Drug Discov Today. 2015 Apr;20(4):393-8
pubmed: 25220442
J Pharmacol Exp Ther. 2018 Sep;366(3):410-421
pubmed: 29914877
Per Med. 2005 Nov;2(4):325-337
pubmed: 29788578
Oncotarget. 2018 Apr 10;9(27):18682-18697
pubmed: 29721153
Biomaterials. 2016 Oct;104:247-57
pubmed: 27472162
Chembiochem. 2016 Apr 1;17(7):570-5
pubmed: 26895508
N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Front Oncol. 2013 Aug 27;3:216
pubmed: 23986882
Curr Protein Pept Sci. 2018;19(10):948-957
pubmed: 28847290
Nat Rev Clin Oncol. 2018 Oct;15(10):599-616
pubmed: 30061739
Hepatology. 2018 Jul;68(1):103-112
pubmed: 29281854
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Clin Res Hepatol Gastroenterol. 2013 Sep;37(4):322-7
pubmed: 23876350
Front Oncol. 2015 Feb 16;5:21
pubmed: 25763353
J Pathol. 2012 Jan;226(1):50-60
pubmed: 22025255
Oncotarget. 2018 Jan 9;9(12):10784-10807
pubmed: 29535843
J Clin Pathol. 2016 Oct;69(10):846-51
pubmed: 26969740
Tumour Biol. 2017 May;39(5):1010428317701628
pubmed: 28468593
J Control Release. 2017 Aug 28;260:142-153
pubmed: 28603028
Angew Chem Int Ed Engl. 2021 Jul 26;60(31):17018-17027
pubmed: 33908690
Eur J Med Chem. 2021 Nov 15;224:113690
pubmed: 34256124
Molecules. 2018 May 16;23(5):
pubmed: 29772690
J Control Release. 2019 Aug 28;308:109-118
pubmed: 31255690
Oncogene. 2011 Jun 2;30(22):2504-13
pubmed: 21297667
Front Oncol. 2014 Dec 11;4:347
pubmed: 25566494
J Ethnopharmacol. 1989 Sep;26(2):147-62
pubmed: 2689797
Curr Protein Pept Sci. 2012 May;13(3):211-23
pubmed: 22612781
Cancer Res. 2008 Sep 1;68(17):7210-8
pubmed: 18757437
J Nanobiotechnology. 2019 Dec 7;17(1):120
pubmed: 31812165
N Engl J Med. 2018 Jul 05;379(1):54-63
pubmed: 29972759
J Clin Invest. 2013 Oct;123(10):4144-57
pubmed: 23999433
N Engl J Med. 2019 Apr 11;380(15):1450-1462
pubmed: 30970190
Molecules. 2020 Feb 13;25(4):
pubmed: 32069856
Ann Surg Oncol. 2011 Aug;18(8):2210-7
pubmed: 21308485
Biochim Biophys Acta. 2003 Mar 17;1603(2):99-111
pubmed: 12618310
J Hepatol. 2012 Mar;56(3):686-95
pubmed: 21971559
Anticancer Agents Med Chem. 2011 Jan;11(1):38-46
pubmed: 21288198
Haematologica. 2012 Apr;97(4):543-50
pubmed: 22133779
Cancer Sci. 2010 May;101(5):1226-33
pubmed: 20331621
Clin Cancer Res. 2015 Jan 15;21(2):347-56
pubmed: 25388166
Ann Hematol. 2012 Feb;91(2):193-201
pubmed: 21720744
Clin Cancer Res. 2014 Apr 15;20(8):2092-103
pubmed: 24436473
J Control Release. 2015 Aug 28;212:59-69
pubmed: 26071630
Lancet. 2017 Jan 7;389(10064):56-66
pubmed: 27932229
Autoimmun Rev. 2021 Sep;20(9):102892
pubmed: 34229046
J Am Soc Nephrol. 1998 Oct;9(10):1873-80
pubmed: 9773788
Cancer Lett. 2000 Dec 8;161(1):89-95
pubmed: 11078917
Liver Int. 2011 Jul;31(6):792-801
pubmed: 21645209
Nat Genet. 2015 May;47(5):505-511
pubmed: 25822088
J Struct Biol. 2013 May;182(2):78-86
pubmed: 23462097
Oncotarget. 2016 Jan 5;7(1):638-55
pubmed: 26575017
Oncology. 2016;90(4):215-20
pubmed: 26974336
Adv Drug Deliv Rev. 2017 Feb;110-111:3-12
pubmed: 27040947
Nanoscale. 2016 Apr 28;8(17):9096-101
pubmed: 26646247
Gastroenterology. 2021 Sep;161(3):879-898
pubmed: 34126063
J Integr Oncol. 2016 Oct;5(4):
pubmed: 28580457
Oncogene. 2016 Sep 15;35(37):4891-902
pubmed: 26876205
N Engl J Med. 2011 Sep 22;365(12):1118-27
pubmed: 21992124
Cancer Cell. 2009 Dec 8;16(6):510-20
pubmed: 19962669
Oncologist. 2020 Mar;25(3):e512-e519
pubmed: 32162815
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16157-62
pubmed: 19805273
Oncogene. 2006 Oct 19;25(49):6447-56
pubmed: 16878161
J Exp Clin Cancer Res. 2019 Apr 11;38(1):156
pubmed: 30975211
Cancers (Basel). 2019 Sep 10;11(9):
pubmed: 31510063
Biomaterials. 2018 Jun;166:52-63
pubmed: 29544111
Nat Rev Dis Primers. 2021 Jan 21;7(1):6
pubmed: 33479224
Nat Rev Dis Primers. 2016 Apr 14;2:16018
pubmed: 27158749
Eur J Histochem. 2018 Sep 18;62(3):
pubmed: 30223640
Int J Oncol. 2015 Mar;46(3):1007-17
pubmed: 25573072