Chlorin e6 Phospholipid Delivery System Featuring APN/CD13 Targeting Peptides: Cell Death Pathways, Cell Localization, In Vivo Biodistribution.

aminopeptidase N/CD13 apoptosis cell-penetrating peptide chlorin e6 colocalization heptaarginine phospholipid nanoparticles photosensitizer targeted drug delivery tumor

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
18 Oct 2022
Historique:
received: 19 08 2022
revised: 07 10 2022
accepted: 17 10 2022
entrez: 27 10 2022
pubmed: 28 10 2022
medline: 28 10 2022
Statut: epublish

Résumé

We have previously designed a phospholipid delivery system for chlorin e6 to increase the efficacy of photodynamic therapy involving a second-generation photosensitizer. Further research into the matter led to double modification of the obtained nanoparticles with ligands exhibiting targeting and cell-penetrating effects: an NGR-containing peptide and heptaarginine (R7), respectively. This study investigated the cell death pathway on HT-1080 tumor cells after treatment with the proposed compositions: the chlorin e6 phospholipid composition and the two-peptide chlorin e6 phospholipid composition. It was demonstrated that most of the cells died by apoptosis. Colocalization analysis of chlorin e6 in the phospholipid composition with two peptides showed mitochondria are one of the targets of the photosensitizer. An HT-1080 tumor-bearing mouse model was used to evaluate the biodistribution of the drug in tumor, liver, and kidney tissues after administration of the study compositions in comparison with free chlorin e6. The photosensitizer mostly accumulated in the tumor tissue of mice administered the phospholipid compositions, and accumulation was increased 2-fold with the peptide-containing composition and approximately 1.5-fold with the unenhanced composition, as compared with free chlorin e6. The enhancement of the chlorin e6 phospholipid composition with targeting and cell-penetrating peptides was found to be effective both in vitro and in vivo.

Identifiants

DOI: 10.3390/pharmaceutics14102224 PMID: 36297658 PMC: PMC9610949
pubmed: 36297658
pii: pharmaceutics14102224
doi: 10.3390/pharmaceutics14102224
pmc: PMC9610949
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : The Ministry of Education and Science of the Russian Federation
ID : 122030100170-5

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Auteurs

Yulia A Tereshkina (YA)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.

Lyubov V Kostryukova (LV)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.
ORCID: 0000-0002-1607-2936

Elena G Tikhonova (EG)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.

Yulia Yu Khudoklinova (YY)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.
ORCID: 0000-0002-7197-3753

Nadezhda A Orlova (NA)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.

Alisa M Gisina (AM)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.

Galina E Morozevich (GE)

Institute of Biomedical Chemistry, 10 Pogodinskaya St., 119121 Moscow, Russia.

Pavel A Melnikov (PA)

V. Serbsky National Medical Research Center for Psychiatry and Narcology, V. Serbsky National Medical Research Center for Psychiatry and Narcology, 23, Kropotkinsky Lane, 119034 Moscow, Russia.

Vadim S Pokrovsky (VS)

Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, 23 Kashirskoe Shosse St., 115478 Moscow, Russia.

Classifications MeSH