Design and characterization of a novel tumor-homing cell-penetrating peptide for drug delivery in TGFBR3 high-expressing tumors.
Type III transforming growth factor β receptor (TGFBR3)
apoptosis
bone morphogenetic protein 4 (BMP4)
trichosanthin (TCS)
tumor-homing cell-penetrating peptide
Journal
Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
03
06
2023
received:
22
02
2023
accepted:
14
08
2023
medline:
9
11
2023
pubmed:
25
8
2023
entrez:
24
8
2023
Statut:
ppublish
Résumé
Targeted therapy has attracted more and more attention in cancer treatment in recent years. However, due to the diversity of tumor types and the mutation of target sites on the tumor surface, some existing targets are no longer suitable for tumor therapy. In addition, the long-term administration of a single targeted drug can also lead to drug resistance and attenuate drug potency, so it is important to develop new targets for tumor therapy. The expression of Type III transforming growth factor β receptor (TGFBR3) is upregulated in colon, breast, and prostate cancer cells, and plays an important role in the occurrence and development of these cancers, so TGFBR3 may be developed as a novel target for tumor therapy, but so far there is no report on this research. In this study, the structure of bone morphogenetic protein 4 (BMP4), one of the ligands of TGFBR3 was analyzed through the docking analysis with TGFBR3 and sequence charge characteristic analysis, and a functional tumor-targeting penetrating peptide T3BP was identified. The results of fluorescent labeling experiments showed that T3BP could target and efficiently enter tumor cells with high expression of TGFBR3, especially A549 cells. When the expression of TGFBR3 on the surface of tumor cells (HeLa) was knocked down by RNA interference, the high delivery efficiency of T3BP was correspondingly reduced by 40%, indicating that the delivery was TGFBR3-dependent. Trichosanthin (TCS, a plant-derived ribosome inactivating protein) fused with T3BP can enhance the inhibitory activity of the fusion protein on A549 cells by more than 200 times that of TCS alone. These results indicated that T3BP, as a novel targeting peptide that can efficiently bind TGFBR3 and be used for targeted therapy of tumors with high expression of TGFBR3. This study enriches the supply of tumor-targeting peptides and provides a new potential application option for the treatment of tumors with high expression of TGFBR3.
Substances chimiques
betaglycan
145170-29-2
Cell-Penetrating Peptides
0
Receptors, Transforming Growth Factor beta
0
Proteoglycans
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1421-1434Informations de copyright
© 2023 John Wiley & Sons Ltd.
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