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.