1 research outputs found
Extra-Large Pore Mesoporous Silica Nanoparticles for Directing in Vivo M2 Macrophage Polarization by Delivering IL‑4
Over
the past decade, mesoporous silica nanoparticles (MSNs) smaller than
200 nm with a high colloidal stability have been extensively studied
for systemic drug delivery. Although small molecule delivery via MSNs
has been successful, the encapsulation of large therapeutic biomolecules,
such as proteins or DNA, is limited due to small pore size of the
conventional MSNs obtained by soft-templating. Here, we report the
synthesis of mesoporous silica nanoparticles with extra-large pores
(XL-MSNs) and their application to in vivo cytokine delivery for macrophage
polarization. Uniform, size-controllable XL-MSNs with 30 nm extra-large
pores were synthesized using organic additives and inorganic seed
nanoparticles. XL-MSNs showed significantly higher loadings for the
model proteins with different molecular weights compared to conventional
small pore MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing
cytokine and very quickly degraded in vivo, to macrophages and polarize
them to anti-inflammatory M2 macrophages in vivo. XL-MSNs induced
a low level of reactive oxygen species (ROS) production and no pro-inflammatory
cytokines in bone marrow-derived macrophages (BMDMs) and in mice injected
intravenously with XL-MSNs. We found that the injected XL-MSNs were
targeted to phagocytic myeloid cells, such as neutrophils, monocytes,
macrophages, and dendritic cells. Finally, we demonstrated that the
injection of IL-4-loaded XL-MSNs successfully triggered M2 macrophage
polarization in vivo, suggesting the clinical potential of XL-MSNs
for modulating immune systems via targeted delivery of various cytokines