Fluorescent RGD-based pro-apoptotic peptide conjugates as mitochondria-targeting probes for enhanced anticancer activities.
Biomed Pharmacother
; 127: 110179, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32387862
ABSTRACT
We have designed 2-domain anticancer peptides with RGD-based KLAK bi-functional short motifs (linear and cyclic analogues). RGD tripeptide acts as tumor blood vessel 'homing' motif while KLAK tetrapeptide internalized in mitochondria and causes cell apoptosis. All three peptides (RGDKLAK; HM, cyclic-RGDKLAK; HMC-1, and RGD-cyclic-KLAK; HMC-2) were conjugated with fluorescein isothiocyanate isomer-I (5-FITC; F) for in-vivo and in-vitro optical imaging studies. These fluorescent-peptide (FL-peptide) analogues were analyzed to possess αvß3-integrin targeting affinity, high uptake in in-vitro cell binding assays followed by in-vivo tumor xenograft mice studies. Pharmacological profile reveals that F-HMC-1 analogue exhibited selectively and specifically higher affinity for αvß3-integrin than other analogues in U87MG cells in comparison with HeLa cells. The subcutaneous U87MG tumor xenograft mice models clearly visualized the uptake of F-HMC-1 in tumor tissue in contrast with normal tissues with tumor-to-normal tissue ratio (T/NTâ¯=â¯15.9⯱â¯1.1) at 2â¯h post-injection. These results suggested that F-HMC-1 peptide has potential diagnostic applications for targeting αvß3-integrin assessed by optical imaging study in U87MG tumor xenograft mice models.
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MEDLINE
Assunto principal:
Oligopeptídeos
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Neoplasias Encefálicas
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Glioblastoma
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Antineoplásicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article