免疫治療法是近年逐漸興起的療法之一，對比傳統的光熱、光動力療法，不僅能有效率的殺死癌症細胞，對於轉移性細胞也能有成功抑制的作用。然而如何成功誘導免疫細胞活化，便是科學家們努力的目標。在本篇研究中，我們成功將醣類聚合在金奈米粒子表面上，並透過儀器的鑑定，確認表面上的醣行為表現。
緊接著我們也將材料應用在誘導腫瘤相關巨噬細胞活化，並與傳統的醣化奈米粒子比較，我們合成出的奈米粒子隨著加入越多的醣劑量，誘導的效率也跟著提升。最後我們也希望能透過我們的材料在未來針對老鼠的腫瘤進行治療，並結合免疫檢查點抗體限制原生性腫瘤的生長、與轉移性腫瘤的復發。

Glyco-nanoparticles are common for targeting either the macrophages or dendritic cell for inducing the immunotherapy. However, most of the literatures didn’t show the good activation of the immunotherapy. That’s why we try to improve the researches. Finally, we successfully synthesized the Au@ONPG with sugar coating and good stability.
Furthermore, we took a series of test for coculturing our materials with tumor-associated macrophages. Due to the high amount of the sugar coating, our materials can efficiently reverse the tumor-associated macrophages to M1-like macrophages, and activated the immune system. In the future, we would to apply our materials to animal’s tumor model and combined with immune check-point blockade for synergistic cancer immunotherapy.

1. Burnet, F. M., Cancer a Biological Approach. BMJ 1957, 1, 841-847.
2. R., S. A.; P., B. S., USE OF TUMOR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 IN THE IMMUNITHERAPY OF PATIENTS WITH METASTATIC MELANOMA. THE NEW ENGLAND JOURNAL MEDICINE 1988, 1676-1680.
3. La-Beck, N. M.; Gabizon, A. A., Nanoparticle Interactions with the Immune System: Clinical Implications for Liposome-Based Cancer Chemotherapy. Front Immunol 2017, 8, 416.
4. Kim, H. S.; Lee, D. Y., Near-Infrared-Responsive Cancer Photothermal and Photodynamic Therapy Using Gold Nanoparticles. Polymers (Basel) 2018, 10 (9).
5. Li, C.; Zhang, Y.; Li, Z.; Mei, E.; Lin, J.; Li, F.; Chen, C.; Qing, X.; Hou, L.; Xiong, L.; Hao, H.; Yang, Y.; Huang, P., Light-Responsive Biodegradable Nanorattles for Cancer Theranostics. Adv Mater 2018, 30 (8).
6. Fan, W.; Huang, P.; Chen, X., Overcoming the Achilles' heel of photodynamic therapy. Chem Soc Rev 2016, 45 (23), 6488-6519.
7. Zhang, D.; Wu, T.; Qin, X.; Qiao, Q.; Shang, L.; Song, Q.; Yang, C.; Zhang, Z., Intracellularly Generated Immunological Gold Nanoparticles for Combinatorial Photothermal Therapy and Immunotherapy against Tumor. Nano Lett 2019, 19 (9), 6635-6646.
8. Zhang, Y.; Wu, L.; Li, Z.; Zhang, W.; Luo, F.; Chu, Y.; Chen, G., Glycocalyx-Mimicking Nanoparticles Improve Anti-PD-L1 Cancer Immunotherapy through Reversion of Tumor-Associated Macrophages. Biomacromolecules 2018, 19 (6), 2098-2108.
9. Meng, X.; Huang, Z.; Teng, F.; Xing, L.; Yu, J., Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev 2015, 41 (10), 868-76.
10. Altarac, S.; Papes, D., Use of D-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women. BJU Int 2014, 113 (1), 9-10.
11. Sihra, N.; Goodman, A.; Zakri, R.; Sahai, A.; Malde, S., Nonantibiotic prevention and management of recurrent urinary tract infection. Nat Rev Urol 2018, 15 (12), 750-776.
12. Barras, A.; Martin, F. A.; Bande, O.; Baumann, J. S.; Ghigo, J. M.; Boukherroub, R.; Beloin, C.; Siriwardena, A.; Szunerits, S., Glycan-functionalized diamond nanoparticles as potent E. coli anti-adhesives. Nanoscale 2013, 5 (6), 2307-16.
13. Doan, V. M.; Chen, C.; Lin, X.; Nguyen, V. P.; Nong, Z.; Li, W.; Chen, Q.; Ming, J.; Xie, Q.; Huang, R., Yulangsan polysaccharide improves redox homeostasis and immune impairment in D-galactose-induced mimetic aging. Food Funct 2015, 6 (5), 1712-8.
14. Ma, J.; Wang, H.; Liu, B.; Shan, Y.; Zhou, H.; Qi, X.; Wu, W.; Jia, L., Combination of chick embryo and nutrient mixture prevent D-galactose-induced cognitive deficits, immune impairment and oxidative stress in aging rat model. Sci Rep 2019, 9 (1), 4092.
15. Son, S.; Nam, J.; Zenkov, I.; Ochyl, L. J.; Xu, Y.; Scheetz, L.; Shi, J.; Farokhzad, O. C.; Moon, J. J., Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination. Nano Lett 2020, 20 (3), 1499-1509.
16. Li, Z.; Sun, L.; Zhang, Y.; Dove, A. P.; O'Reilly, R. K.; Chen, G., Shape Effect of Glyco-Nanoparticles on Macrophage Cellular Uptake and Immune Response. ACS Macro Lett 2016, 5 (9), 1059-1064.
17. Lin, M.; Zhang, Y.; Chen, G.; Jiang, M., Supramolecular Glyco-nanoparticles Toward Immunological Applications. Small 2015, 11 (45), 6065-70.
18. Su, L.; Zhang, W.; Wu, X.; Zhang, Y.; Chen, X.; Liu, G.; Chen, G.; Jiang, M., Glycocalyx-Mimicking Nanoparticles for Stimulation and Polarization of Macrophages via Specific Interactions. Small 2015, 11 (33), 4191-200.
19. Wu, L.; Zhang, Y.; Li, Z.; Yang, G.; Kochovski, Z.; Chen, G.; Jiang, M., "Sweet" Architecture-Dependent Uptake of Glycocalyx-Mimicking Nanoparticles Based on Biodegradable Aliphatic Polyesters by Macrophages. J Am Chem Soc 2017, 139 (41), 14684-14692.
20. Meriem, M.; Rosa, E. F.; Roberta, M.; Francois, B.; Michel, T.; Rosa, L.; Cedric, L.; Jean-Pierre, S.; Franck, F.; Antonio, M.; Alba, S., Human Macrophage Galactose-Type Lectin (MGL)
Recognizes the Outer Core of Escherichia coli
Lipooligosaccharide. ChemBioChem 2019, 20, 1778 – 1782.
21. Liu, J.; Qin, G.; Raveendran, P.; Ikushima, Y., Facile "green" synthesis, characterization, and catalytic function of beta-D-glucose-stabilized Au nanocrystals. Chemistry 2006, 12 (8), 2131-8.
22. Roa, W.; Zhang, X.; Guo, L.; Shaw, A.; Hu, X.; Xiong, Y.; Gulavita, S.; Patel, S.; Sun, X.; Chen, J.; Moore, R.; Xing, J. Z., Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle. Nanotechnology 2009, 20 (37), 375101.
23. Yi, Y.; Kim, H. J.; Zheng, M.; Mi, P.; Naito, M.; Kim, B. S.; Min, H. S.; Hayashi, K.; Perche, F.; Toh, K.; Liu, X.; Mochida, Y.; Kinoh, H.; Cabral, H.; Miyata, K.; Kataoka, K., Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells. J Control Release 2019, 295, 268-277.
24. Jiang, X.; Xin, H.; Ren, Q.; Gu, J.; Zhu, L.; Du, F.; Feng, C.; Xie, Y.; Sha, X.; Fang, X., Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment. Biomaterials 2014, 35 (1), 518-29.
25. Gan, J.; Dou, Y.; Li, Y.; Wang, Z.; Wang, L.; Liu, S.; Li, Q.; Yu, H.; Liu, C.; Han, C.; Huang, Z.; Zhang, J.; Wang, C.; Dong, L., Producing anti-inflammatory macrophages by nanoparticle-triggered clustering of mannose receptors. Biomaterials 2018, 178, 95-108.
26. Ngambenjawong, C.; Gustafson, H. H.; Pun, S. H., Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliv Rev 2017, 114, 206-221.
27. Lin, Y.; Xu, J.; Lan, H., Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol 2019, 12 (1), 76.
28. Zhang, F.; Parayath, N. N.; Ene, C. I.; Stephan, S. B.; Koehne, A. L.; Coon, M. E.; Holland, E. C.; Stephan, M. T., Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat Commun 2019, 10 (1), 3974.
29. Vergadi, E.; Ieronymaki, E.; Lyroni, K.; Vaporidi, K.; Tsatsanis, C., Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization. J Immunol 2017, 198 (3), 1006-1014.
30. Carrillo-Conde, B.; Song, E. H.; Chavez-Santoscoy, A.; Phanse, Y.; Ramer-Tait, A. E.; Pohl, N. L.; Wannemuehler, M. J.; Bellaire, B. H.; Narasimhan, B., Mannose-functionalized "pathogen-like" polyanhydride nanoparticles target C-type lectin receptors on dendritic cells. Mol Pharm 2011, 8 (5), 1877-86.
31. Cui, L.; Cohen, J. A.; Broaders, K. E.; Beaudette, T. T.; Frechet, J. M., Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting. Bioconjug Chem 2011, 22 (5), 949-57.
32. Flores-Mireles, A. L.; Walker, J. N.; Caparon, M.; Hultgren, S. J., Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol 2015, 13 (5), 269-84.
33. Kappala, D.; Sarkhel, R.; Dixit, S. K.; Lalsangpuii; Mahawar, M.; Singh, M.; Ramakrishnan, S.; Goswami, T. K., Role of different receptors and actin filaments on Salmonella Typhimurium invasion in chicken macrophages. Immunobiology 2018, 223 (6-7), 501-507.
34. Terlizzi, M. E.; Gribaudo, G.; Maffei, M. E., UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies. Front Microbiol 2017, 8, 1566.
35. Yang, R.; Xu, J.; Xu, L.; Sun, X.; Chen, Q.; Zhao, Y.; Peng, R.; Liu, Z., Cancer Cell Membrane-Coated Adjuvant Nanoparticles with Mannose Modification for Effective Anticancer Vaccination. ACS Nano 2018, 12 (6), 5121-5129.
36. Karatas, O. F.; Sezgin, E.; Aydin, O.; Culha, M., Interaction of gold nanoparticles with mitochondria. Colloids Surf B Biointerfaces 2009, 71 (2), 315-8.