Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Exp Mol Med ; 55(6): 1099-1109, 2023 06.
Article in English | MEDLINE | ID: mdl-37258584

ABSTRACT

Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide-drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein-protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Peptides/therapeutic use , Peptides/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Receptors, Cell Surface , Hormones
2.
Theranostics ; 11(3): 1326-1344, 2021.
Article in English | MEDLINE | ID: mdl-33391537

ABSTRACT

CD44v6, a splice variant of the cell surface glycoprotein CD44, acts as a co-receptor for c-Met and is upregulated in tumors with high metastatic potential. Methods: We screened a phage-displayed peptide library for peptides that selectively bind to CD44v6-overexpressing cells and exploited them to block CD44v6 and deliver a pro-apoptotic peptide to tumors for cancer therapy. Results: CNLNTIDTC (NLN) and CNEWQLKSC (NEW) peptides bound preferentially to CD44v6-high cells than to CD44v6-low cells. The binding affinities of NLN and NEW to CD44v6 protein were 253 ± 79 and 85 ± 18 nM, respectively. Peptide binding to CD44v6-high cells was inhibited by the knockdown of CD44v6 gene expression and competition with an anti-CD44v6 antibody. A pull-down assay with biotin-labeled peptides enriched CD44v6 from cell lysates. NLN and NEW induced CD44v6 internalization and inhibited hepatocyte growth factor-induced c-Met internalization, c-Met and Erk phosphorylation, and cell migration and invasion. In mice harboring tumors, intravenously administered NLN and NEW homed to the tumors and inhibited metastasis to the lungs. When combined with crizotinib, a c-Met inhibitor, treatment with each peptide inhibited metastatic growth more efficiently than each peptide or crizotinib alone. In addition, KLAKLAKKLAKLAK pro-apoptotic peptide guided by NLN (NLN-KLA) or NEW (NEW-KLA) killed tumor cells and inhibited tumor growth and metastasis. No significant systemic side effects were observed after treatments. Conclusions: These results suggest that NLN and NEW are promising metastasis-inhibiting peptide therapeutics and targeting moieties for CD44v6-expressing metastases.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Hyaluronan Receptors/metabolism , Neoplasm Metastasis/prevention & control , Peptides/pharmacology , Protein Kinase Inhibitors/pharmacology , Animals , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Crizotinib/pharmacology , Female , HEK293 Cells , Hepatocyte Growth Factor/metabolism , Humans , MAP Kinase Signaling System/drug effects , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Proto-Oncogene Proteins c-met/metabolism , Up-Regulation/drug effects
3.
Microb Pathog ; 137: 103784, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31600538

ABSTRACT

Bioluminescence imaging is a non-invasive tool for in vivo real-time monitoring of infectious disease progression in animal models. However, no bioluminescence imaging assay has been developed to monitor Acinetobacter baumannii infections. In the current study, bioluminescent strains of A. baumannii ATCC 17978 and its isogenic ΔompA mutant were constructed by integrating the promoter of the ompA gene and the luxCDABE luciferase gene into the bacterial chromosome. In an acute murine pneumonia model, bioluminescence of the two reporter strains was clearly visible in the lungs and the bioluminescent signal increased over time. Bioluminescence was correlated with bacterial burden and histopathology in reporter strain-infected mice, suggesting that bioluminescent bacteria are useful for monitoring A. baumannii infections in animal models.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/physiology , Luminescent Measurements/methods , Pneumonia/microbiology , Acinetobacter baumannii/chemistry , Acinetobacter baumannii/genetics , Animals , Disease Models, Animal , Female , Humans , Luminescent Proteins/chemistry , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice , Mice, Inbred BALB C
SELECTION OF CITATIONS
SEARCH DETAIL
...