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.