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Chloroquine Assisted Delivery of microRNA Mimic Let-7b to NSCLC Cell Line by PAMAM (G5) - HA Nano-carrier

Author(s):

Niloufar Maghsoudnia, Reza Baradaran Eftekhari, Alireza Naderi Sohi and Farid Abedin Dorkoosh*   Pages 1 - 13 ( 13 )

Abstract:


Aim: Polyamidoamine (PAMAM) dendrimers are attracting scientists’ interest as vehicles for nucleic acid delivery due to their suitable properties. The highly positive surface charged of PAMAM enables adequate interaction with negative-ly charged microRNAs.

Objective: 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. In order to increase the anti-tumor effect, chlo-roquine 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 retarda-tion, cellular uptake, cell viability and gene expression studies were investigated for the designed delivery system.

Methods: 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 up-take study, NPs labeled with Fluorescein isothiocyanate (FITC), were successfully taken up in cancer cells.

Results: Moreover, ex-pression study of three genes linked with cancer initiation and development in NSCLC, including KRAS, p-21, and BCL-2 indicated 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, the fact which has frequently been highlighted by many re-searchers upon the potentials of micro RNA delivery in cancer cells.

Keywords:

Gene-delivery, NSCLC, PAMAM dendrimers, microRNA let-7b, Chloroquine

Affiliation:

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran



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