Chloroquine Assisted Delivery of microRNA Mimic Let-7b to NSCLC Cell Line by PAMAM (G5) - HA Nano-Carrier.
Curr Drug Deliv
; 18(1): 31-43, 2021.
Article
em En
| MEDLINE
| ID: mdl-32753014
ABSTRACT
AIM:
Polyamidoamine (PAMAM) dendrimers are attracting interest of the scientists as vehicles for nucleic acid delivery due to their suitable properties. The highly positive surface charged of PAMAM enables an adequate interaction with negatively charged microRNAs.PURPOSE:
The purpose of this study is to investigate the anti-tumor effect of microRNA Mimic let-7b loaded in PAMAM dendrimers (G5) on Non-Small Cell Lung Cancer (NSCLC) cells.OBJECTIVE:
In order to increase the anti-tumor effect, chloroquine is employed to enhance the endosomal escape which is counted as a limitation in the advancement of gene delivery. Nanoparticles (NPs) were coated with natural polysaccharide "Hyaluronic Acid (HA)" to develop biodegradable carriers with targeting moiety for over-expressed CD44 receptors on NSCLC cells. The size and zeta potential measurements, gel retardation, cellular uptake, cell viability and gene expression studies were investigated for the designed delivery system.RESULTS:
DLS analysis showed monodispersed small nanoparticles, which was in agreement with TEM results. Remarkably, NPs in the cells pretreated with chloroquine exhibited the highest cytotoxicity and were capable of inducing apoptosis. In cellular uptake study, NPs labeled with Fluorescein Isothiocyanate (FITC), were successfully taken up in cancer cells. Moreover, the expression study of three genes linked with cancer initiation and development in NSCLC, including KRAS, p-21, and BCL-2 indicated a decrease in KRAS and BCL-2 (oncogenic and anti-apoptotic genes) and increase in p-21 (apoptotic gene).CONCLUSION:
All factors considered, the results declare that application of let-7b-loaded PAMAM-HA NPs in combination with chloroquine can be a promising therapeutic option in cancer cells inhibition. This fact has frequently been highlighted by many researchers upon the potentials of micro RNA delivery in cancer cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliaminas
/
Cloroquina
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Carcinoma Pulmonar de Células não Pequenas
/
MicroRNAs
/
Dendrímeros
/
Ácido Hialurônico
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Curr Drug Deliv
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irã