CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies for KRAS silencing in cancer treatment.
Biguanides
/ chemistry
Cell Line, Tumor
Chemical Phenomena
Chitosan
/ chemistry
Coculture Techniques
Colorectal Neoplasms
/ genetics
Drug Delivery Systems
/ methods
Drug Liberation
Drug Stability
Fibroblasts
/ metabolism
Gene Silencing
Humans
Hyaluronan Receptors
/ metabolism
Hyaluronic Acid
/ chemistry
Nanomedicine
/ methods
Nanoparticles
/ metabolism
Proto-Oncogene Proteins p21(ras)
/ deficiency
RNA, Small Interfering
/ administration & dosage
CD44
Hyaluronan
KRAS
Polymer therapeutics
siRNA
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
20 Apr 2019
20 Apr 2019
Historique:
received:
11
12
2018
revised:
21
01
2019
accepted:
18
02
2019
pubmed:
2
3
2019
medline:
20
8
2019
entrez:
2
3
2019
Statut:
ppublish
Résumé
KRAS is a small GTPase that regulates cell proliferation and survival. In tumors, the KRAS gene is mutated, and leading to unregulated tumor growth. Despite the recognized importance of KRAS in cancer, attempts to develop small molecule inhibitors have proved unsuccessful. An alternative strategy is gene silencing and the use of small nucleic acid sequences (e.g. siRNA, shRNA), has been reported to successfully downregulate KRAS. In this study we developed ternary nanocomplexes to deliver an anti-KRAS siRNA to colorectal cancer cells, exploiting the interaction of hyaluronic acid (HA) with CD44 as a means to achieve selective targeting of CD44-positive cancer cells. Two different polycations, poly(hexamethylene biguanide) and chitosan, were complexed with siRNA and coated with HA. Physico-chemical properties and stability of nanoparticles were characterized, including size, surface charge, and degree of siRNA protection. We demonstrate nanoparticle internalization (flow cytometry), siRNA cytosolic release (confocal microscopy) and KRAS silencing (RT-qPCR) in CD44
Identifiants
pubmed: 30822503
pii: S0378-5173(19)30155-3
doi: 10.1016/j.ijpharm.2019.02.032
pii:
doi:
Substances chimiques
Biguanides
0
Hyaluronan Receptors
0
KRAS protein, human
0
RNA, Small Interfering
0
polihexanide
322U039GMF
Hyaluronic Acid
9004-61-9
Chitosan
9012-76-4
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Pagination
114-123Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.