課題番号 ：S-15-NM-0048
利用形態 ：共同研究
利用課題名（日本語） ：
Program Title (English) ：Mesoporous nanoparticles for CpG delivery
利用者名（日本語） ：
Username (English) ：Yufang Zhu1)
所属名（日本語） ：
Affiliation (English) ：1) University of Shanghai for Science and Technology

１．概要（Summary ）
Mesoporous silica nanoparticles are promising carriers for delivering drugs/genes. CpG oligodeoxynucleotides as a potent immunostimulator can induce innate and adaptive immune response through their recognition by TLR9, a molecule located in the endolysosomes of B cells and antigen-presenting cells (APCs), which can be used in immunotherapy for various illnesses including cancer, allergies/asthma, and infectious diseases. In this program, we prepared mesoporous silica nanoparticles, and developed a potential CpG delivery system based on mesoporous silica nanoparticles for enhancing the delivery efficiency.

２．実験（Experimental）
In this program, we tested in vitro cytotoxicity, cell uptake of mesoporous silica nanoparticles using WST-8 assay and CLSM observation. On the other hand, we also tested cytokine induction (IL-6, IFN-α) using RT-PCR. The detailed experimental methods are described in the published papers.

３．結果と考察（Results and Discussion）
(1) We investigated the effects of amino groups of mesoporous silica nanoparticles on CpG ODN delivery efficiency. The results indicated that the MSN-NH2/CpG, MSN-2NH2/CpG and MSN-3NH2/CpG complexes exhibited different CpG ODN delivery efficiency, and the MSN-NH2/CpG complexes had the highest ability to induce IL-6 secretion. (Y. Xu, et al. Sci. Technol. Adv. Mater. 2015, 16, 045006 (11pp)).
(2) We investigated the effects of particle size of dendritic mesoporous silica nanoparticles on the CpG ODN delivery efficiency. The results indicated that CpG ODNs were bonded to the aminated nanoparticles to form DMSN97-NH2/CpG, DMSN205-NH2/CpG and DMSN535-NH2/CpG complexes. All of complexes were taken up by cells and were located in endolysosomes. Also, three kinds of complexes significantly enhanced IL-6 induction compared to free CpG ODNs, but the DMSN97-NH2/CpG complexes exhibited the highest IL-6 induction ability. (Y. Xu, et al. Mater. Express, 2016, in press).

４．その他・特記事項（Others）
We thank Morita-san and Xianglan Li-san for helping conduct the experiments on cytotoxicity cell uptake and cytokine induction. We thank Prof. Nobutaka Hanagata for discussing the experimental data and paper revision.

５．論文・学会発表（Publication/Presentation）
[1] Yi Xu, Peter Claiden, Yufang Zhu*, Hiromi Morita, Nobutaka Hanagata, Effect of amino groups of mesoporous silica nanoparticles on CpG oligodexynucleotide delivery. Sci. Technol. Adv. Mater. 2015, 16, 045006(11pp).
[2] Yi Xu, Yufang Zhu*, Xianglan Li, Hiromi Morita, Nobutaka Hanagata*. Investigation of dendritic mesoporous silica nanoparticles for cytosine-phosphate-guanosine oligodexynucleotide delivery. Materials Express, 2016, DOI:10.1166/mex.2016.1288.

６．関連特許（Patent）