Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides
Despite continuous advances, anticancer therapy still faces several technical hurdles, such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, trimethine cyanine dye, and folate to target the mit...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/5/725 |
| _version_ | 1797501230117814272 |
|---|---|
| author | Davide Cardella Wenjing Deng Louis Y. P. Luk Yu-Hsuan Tsai |
| author_facet | Davide Cardella Wenjing Deng Louis Y. P. Luk Yu-Hsuan Tsai |
| author_sort | Davide Cardella |
| collection | DOAJ |
| description | Despite continuous advances, anticancer therapy still faces several technical hurdles, such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, trimethine cyanine dye, and folate to target the mitochondria of tumor cells. A series of proapoptotic peptides and their conjugates with a cyanine dye and/or folate were synthesized in the solid phase, and their toxicity in different human cell lines was assessed. Cyanine-bearing conjugates were found to be up to 100-fold more cytotoxic than the parent peptides and to localize in mitochondria. However, the addition of a folate motif did not enhance the potency or selectivity of the resulting conjugates toward tumor cells that overexpress folate receptor α. Furthermore, while dual-labeled constructs were also found to localize within the target organelle, they were not generally selective towards folate receptor α-positive cell lines in vitro. |
| first_indexed | 2024-03-10T03:15:23Z |
| format | Article |
| id | doaj.art-45f54fc5eb294ea8949ac11ff8bf3a6f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T03:15:23Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-45f54fc5eb294ea8949ac11ff8bf3a6f2023-11-23T10:14:41ZengMDPI AGBiomolecules2218-273X2022-05-0112572510.3390/biom12050725Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic PeptidesDavide Cardella0Wenjing Deng1Louis Y. P. Luk2Yu-Hsuan Tsai3School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, UKShenzhen Bay Laboratory, Gaoke Innovation Center, Institute of Molecular Physiology, Guangming District, Shenzhen 518132, ChinaSchool of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, UKDespite continuous advances, anticancer therapy still faces several technical hurdles, such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, trimethine cyanine dye, and folate to target the mitochondria of tumor cells. A series of proapoptotic peptides and their conjugates with a cyanine dye and/or folate were synthesized in the solid phase, and their toxicity in different human cell lines was assessed. Cyanine-bearing conjugates were found to be up to 100-fold more cytotoxic than the parent peptides and to localize in mitochondria. However, the addition of a folate motif did not enhance the potency or selectivity of the resulting conjugates toward tumor cells that overexpress folate receptor α. Furthermore, while dual-labeled constructs were also found to localize within the target organelle, they were not generally selective towards folate receptor α-positive cell lines in vitro.https://www.mdpi.com/2218-273X/12/5/725cancercyanine dyesfolatemitochondriaproapoptotic peptidessolid-phase synthesis |
| spellingShingle | Davide Cardella Wenjing Deng Louis Y. P. Luk Yu-Hsuan Tsai Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides Biomolecules cancer cyanine dyes folate mitochondria proapoptotic peptides solid-phase synthesis |
| title | Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides |
| title_full | Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides |
| title_fullStr | Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides |
| title_full_unstemmed | Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides |
| title_short | Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides |
| title_sort | effect of trimethine cyanine dye and folate conjugation on the in vitro biological activity of proapoptotic peptides |
| topic | cancer cyanine dyes folate mitochondria proapoptotic peptides solid-phase synthesis |
| url | https://www.mdpi.com/2218-273X/12/5/725 |
| work_keys_str_mv | AT davidecardella effectoftrimethinecyaninedyeandfolateconjugationontheinvitrobiologicalactivityofproapoptoticpeptides AT wenjingdeng effectoftrimethinecyaninedyeandfolateconjugationontheinvitrobiologicalactivityofproapoptoticpeptides AT louisypluk effectoftrimethinecyaninedyeandfolateconjugationontheinvitrobiologicalactivityofproapoptoticpeptides AT yuhsuantsai effectoftrimethinecyaninedyeandfolateconjugationontheinvitrobiologicalactivityofproapoptoticpeptides |