Narrow Results

Microcapsules that release antigen-capturing nanoparticles (AC-NPs) with macrophage inflammatory protein-3 alpha (MIP-3$\alpha$) and anti-programmed death-1 (PD-1) antibody are developed, and these microcapsules have the ability to enhance immunoresponses through cross-priming of cluster of differentiation 8+ (CD8+) T cells by dendritic cells (DCs) in vivo in BALB/c mice.

Lipid protamine hyaluronic acid nanoparticles containing AC-NPs generated via nanoprecipitation of 4 mg/mL of polylactic-co-glycolic acid (PLGA), 1,000 ng/mL of MIP-3$\alpha$ and 400 $\mu$g of anti-PD-1 were mixed with 1 mL of 4.0% alginate and 3.0% of hyaluronate and then sprayed with 0.5 mM of ferrous chloride. These capsules were injected subcutaneously around LM17 tumor in the left hind legs of BALB/c mice. The tumors were exposed to a radiation dose of 10 or 20 Gy from 100 keV soft X-ray radiation. PLGA AC-NPs and MIP-3$\alpha$ were released in response to the radiation dose.

PLGA AC-NPs captured tumor-derived protein antigens are released by exposure to radiation, and these antigens were transported to DCs that were recruited and activated by MIP-3$\alpha$, intensifying the DC-associated cross-priming of CD8+ T cells. These treatments resulted in increased antitumor effect and reduced metastasis by abscopal effect. Our targeted immunotherapy may lead to better tumor therapy.

This study aimed to investigate the effect of the particles releasing chitosan upon exposure to radiation on inhibition of metastasis.

A 10 mL solution of water containing 0.2% weight/volume alginate, 0.1% hyaluronic acid, and 100-mg chitosan was sprayed into the vibrating solution through a stainless mesh filter (pore size: 0.8 $\mu$m) using an ultrasound disintegrator, thereby generating chitosan particles. Further, $1\times 10^{10}$ particles floating in 0.1 mL normal saline were subcutaneously injected around the 4TI cells-derived tumor in the left hind legs of six-week-old male C3He/N mice. Six hours after injection, tumors were exposed to 10 Gy or 20 Gy of 100-keV soft X-ray radiation. The release of chitosan was expressed as the frequency of ruptured chitosan particles 12 h after radiation. The antimetastatic effect was confirmed by a reduction in the number of metastatic pulmonary nodules 21 days after completion of treatment.

More than $56.3\pm 4.3$% of the chitosan particles released chitosan in response to radiation. The particles releasing chitosan had a prolonged antimetastatic effect when compared with the particles not releasing chitosan, thereby resulting in a significantly greater antimetastatic effect lasting for four weeks since the completion of treatment, in tumors treated with both 10 Gy and 20 Gy of radiation.

Hence, particlizing chitosan could be useful in reducing metastasis in irradiated tumors.