Biodistribution and Activity of EGFR Targeted Polymeric Micelles Delivering a New Inhibitor of DNA Repair to Orthotopic Colorectal Cancer Xenografts with Metastasis.
GE11 peptide
colon cancer
drug delivery
mice imaging
polymeric micelles
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
06 06 2022
06 06 2022
Historique:
pubmed:
11
3
2022
medline:
9
6
2022
entrez:
10
3
2022
Statut:
ppublish
Résumé
The disruption of polynucleotide kinase/phosphatase (PNKP) in colorectal cancer (CRC) cells deficient in phosphatase and tensin homolog (PTEN) is expected to lead to the loss of cell viability by a process known as synthetic lethality. In previous studies, we have reported on the encapsulation of a novel inhibitor of PNKP, namely, A83B4C63, in polymeric micelles and its activity in slowing the growth of PTEN-deficient CRC cells as well as subcutaneous xenografts. In this study, to enhance drug delivery and specificity to CRC tumors, the surface of polymeric micelles carrying A83B4C63 was modified with GE11, a peptide targeting epidermal growth factor receptor (EGFR) overexpressed in about 70% of CRC tumors. Using molecular dynamics (MD) simulations, we assessed the binding site and affinity of GE11 for EGFR. The GE11-modified micelles, tagged with a near-infrared fluorophore, showed enhanced internalization by EGFR-overexpressing CRC cells
Identifiants
pubmed: 35271294
doi: 10.1021/acs.molpharmaceut.1c00918
pmc: PMC9175178
doi:
Substances chimiques
Micelles
0
Polymers
0
PNKP protein, human
EC 2.7.1.-
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1825-1838Subventions
Organisme : CIHR
ID : PJT168869
Pays : Canada
Organisme : CIHR
ID : MOP 159757
Pays : Canada
Organisme : CIHR
ID : MOP 178028
Pays : Canada
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