Dual-targeting SNALPs can efficiently transfect B16F10
melanoma
cells in vitro and display minimal toxicity. B16F10
cells were cultured until 90% confluent before being pulsed with SNALP
formulations (0.75 μg of each type of RNA) for 48 h at 37 °C.
Cells were harvested and doubly stained with fluorescently labeled
anti-mouse OX40L and PDL1 monoclonal antibodies. (A) Shows representative
flow cytometry plots. The conditions are as follows: untransfected,
siPDL1, mOX40L, mOX40L–siNeg (coformulation), mOX40L–siPDL1
(coformulation), and siPDL1 + mOX40L (mixture of two SNALPs). Quadrant
gates were drawn based on isotype control antibody staining, percentage
of cells in each quadrant is inset. (B) Shows the values obtained
for PDL1 silencing, expressed as MFI percentage of control normalized
to 100%. OX40L expression (MFI) is shown in (C). For all the graphs,
error bars correspond to standard error of the mean (SEM). Significance
was examined with one-way ANOVA multiple comparison test (Tukey’s); n = 3–8 repeats for each SNALP formulation. (D) To
assess viability of B16F10 cells after being pulsed with SNALPs or
RNA-free lipid particles an MTT assay was carried out. A 2-fold dilution
series of test formulations was prepared and incubated with cells
for 48 h at 37 °C. Error bars were drawn by standard error of
the mean (SEM) average of n = 10, significance was
tested with a two-way ANOVA: Sidak’s multiple comparison test.
*,p < 0.05.