posted on 2020-09-02, 20:47authored byTaylor
M. Hanley, Raviraj Vankayala, Jenny T. Mac, David D. Lo, Bahman Anvari
Erythrocyte-derived
particles activated by near-infrared (NIR)
light present a platform for various phototheranostic applications.
We have engineered such a platform with indocyanine green as the NIR-activated
agent. A particular feature of these particles is that their diameters
can be tuned from micro- to nanoscale, providing a potential capability
for broad clinical utility ranging from vascular to cancer-related
applications. An important issue related to clinical translation of
these particles is their immunogenic effects. Herein, we have evaluated
the early-induced innate immune response of these particles in healthy
Swiss Webster mice following tail vein injection by measurements of
specific cytokines in blood serum, the liver, and the spleen following
euthanasia. In particular, we have investigated the effects of particle
size and relative dose, time-dependent cytokine response for up to
6 h postinjection, functionalization of the nanosized particles with
folate or Herceptin, and dual injections of the particles 1 week apart.
Mean concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor
(TNF)-α, and monocyte chemoattractant protein (MCP)-1 in response
to injection of microsized particles at the investigated relative
doses were significantly lower than the corresponding mean concentrations
induced by lipopolysaccharide (positive control) at 2 h. All investigated
doses of the nanosized particles induced significantly higher concentrations
of MCP-1 in the liver and the spleen as compared to phosphate buffer
saline (PBS) (negative control) at 2 h. In response to micro- and
nanosized particles at the highest investigated dose, there were significantly
higher levels of TNF-α in blood serum at 2 and 6 h postinjection
as compared to the levels associated with PBS treatment at these times.
Whereas the mean concentration of TNF-α in the liver significantly
increased between 2 and 6 h postinjection in response to the injection
of the microsized particles, it was significantly reduced during this
time interval in response to the injection of the nanosized particles.
In general, functionalization of the nanosized particles was associated
with a reduction of IL-6 and MCP-1 in blood serum, the liver, and
the spleen, and TNF-α in blood serum. With the exception of
IL-10 in the spleen in response to nanosized particles, the second
injection of micro- or nanosized particles did not lead to significantly
higher concentrations of other cytokines at the investigated dose
as compared to a single injection.