Fabrication of anionic dextran-coated micelles for aptamer targeted delivery of camptothecin and survivin-shRNA to colon adenocarcinoma.
Journal
Gene therapy
ISSN: 1476-5462
Titre abrégé: Gene Ther
Pays: England
ID NLM: 9421525
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
10
06
2020
accepted:
26
01
2021
revised:
08
11
2020
pubmed:
27
2
2021
medline:
11
5
2022
entrez:
26
2
2021
Statut:
ppublish
Résumé
In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.
Identifiants
pubmed: 33633357
doi: 10.1038/s41434-021-00234-0
pii: 10.1038/s41434-021-00234-0
doi:
Substances chimiques
Dextrans
0
Micelles
0
Polyesters
0
RNA, Small Interfering
0
Survivin
0
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55-68Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
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