posted on 2013-06-18, 00:00authored byTakaharu Okada, Koichiro Uto, Masao Sasai, Chun Man Lee, Mitsuhiro Ebara, Takao Aoyagi
In this study, we created a nanoscale
layer of hyaluronic acid
(HA) on the inactivated Hemagglutinating Virus of Japan envelope (HVJ-E)
via a layer-by-layer (LbL) assembly technique for CD-44 targeted delivery.
HVJ-E was selected as the template virus because it has shown a tumor-suppressing
ability by eliciting inflammatory cytokine production in dendritic
cells. Although it has been required to increase the tumor-targeting
ability and reduce nonspecific binding because HVJ-E fuses with virtually
all cells and induces hemagglutination in the bloodstream, complete
modifications of single-envelope-type viruses with HA have been difficult.
Therefore, we studied the surface ζ potential of HVJ-E at different
pH values and carefully examined the deposition conditions for the
first layer using three cationic polymers: poly-l-lysine
(PLL), chitosan (CH), and glycol chitosan (GC). GC-coated HVJ-E particles
showed the highest disperse ability under physiological pH and salt
conditions without aggregation. An HA layer was then prepared via
alternating deposition of HA and GC. The successive decoration of
multilayers on HVJ-E has been confirmed by dynamic light scattering
(DLS), ζ potentials, and transmission electron microscopy (TEM).
An enzymatic degradation assay revealed that only the outermost HA
layer was selectively degraded by hyaluronidase. However, entire layers
were destabilized at lower pH. Therefore, the HA/GC-coated HVJ-E describe
here can be thought of as a potential bomb for cancer immunotherapy
because of the ability of targeting CD44 as well as the explosion
of nanodecorated HA/GC layers at endosomal pH while preventing nonspecific
binding at physiological pH and salt conditions such as in the bloodstream
or normal tissues.