Frontiers of Chemical Science and Engineering >
Radial porous SiO2 nanoflowers potentiate the effect of antigen/adjuvant in antitumor immunotherapy
Received date: 28 Aug 2020
Accepted date: 28 Nov 2020
Published date: 15 Oct 2021
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Here, we reported a cancer nanovaccine based on SiO2 nanoflowers with a special radial pore structure, which greatly enhanced cross-presentation and induced the production of cytotoxic T lymphocyte cells secreting granzymes B and interferon-γ. The antigen ovalbumin was covalently conjugated onto the as-synthesized hierarchical SiO2 nanoflowers, and the adjuvant cytosine-phosphate-guanine was electrostatically adsorbed into their radial pore by simple mixing before use. The nanovaccine exhibited excellent storage stability without antigen release after 27 days of incubation, negligible cytotoxicity to dendritic cells, and a high antigen loading capacity of 430 ± 66 mg·g−1 support. Besides, the nanovaccine could be internalized by dendritic cells via multiple pathways. And the enhancement of antigen/adjuvant uptake and lysosome escape of antigen were observed. Noteworthy, in vitro culture of bone marrow-derived dendritic cells in the presence of nanovaccine proved the activation of dendritic cells and antigen cross-presentation as well as secretion of proinflammatory cytokines. Besides, in vivo study verified the targeting of nanovaccine to draining lymph nodes, the complete suppression of tumor in six out of ten mice, and the triggering of notable tumor growth delay. Overall, the present results indicated that the nanovaccine can be served as a potential therapeutic vaccine to treat cancer.
Key words: silica nanoflower; antigen delivery; cancer immunotherapy; nanovaccine
Chuangnian Zhang , Ying Dong , Jing Gao , Xiaoli Wang , Yanjun Jiang . Radial porous SiO2 nanoflowers potentiate the effect of antigen/adjuvant in antitumor immunotherapy[J]. Frontiers of Chemical Science and Engineering, 2021 , 15(5) : 1296 -1311 . DOI: 10.1007/s11705-020-2034-6
1 |
Kelly P N. The cancer immunotherapy revolution. Science, 2018, 359(6382): 1344–1345
|
2 |
Sahin U, Türeci Ö. Personalized vaccines for cancer immunotherapy. Science, 2018, 359(6382): 1355–1360
|
3 |
Nam J, Son S, Park K S, Zou W, Shea L D, Moon J J. Cancer nanomedicine for combination cancer immunotherapy. Nature Reviews. Materials, 2019, 4(6): 398–414
|
4 |
Hollingsworth R E, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines, 2019, 4(1): 7
|
5 |
Wculek S K, Cueto F J, Mujal A M, Melero I, Krummel M F, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nature Reviews. Immunology, 2020, 20(1): 1–18
|
6 |
Hu Z, Ott P A, Wu C J. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nature Reviews. Immunology, 2017, 18(3): 168–182
|
7 |
Riley R S, June C H, Langer R, Mitchell M J. Delivery technologies for cancer immunotherapy. Nature Reviews. Drug Discovery, 2019, 18(3): 175–196
|
8 |
Huang P, Wang X, Liang X, Yang J, Zhang C, Kong D, Wang W. Nano-, micro-, and macroscale drug delivery systems for cancer immunotherapy. Acta Biomaterialia, 2019, 85: 1–26
|
9 |
Newton J M, Sikora A G, Young S. Chapter 41—Materials-Based Cancer Immunotherapies: Principles of Regenerative Medicine. 3rd ed. Boston: Academic Press, 2019, 715–739
|
10 |
Gause K T, Wheatley A K, Cui J, Yan Y, Kent S J, Caruso F. Immunological principles guiding the rational design of particles for vaccine delivery. ACS Nano, 2017, 11(1): 54–68
|
11 |
Gu L. Tailored silica nanomaterials for immunotherapy. ACS Central Science, 2018, 4(5): 527–529
|
12 |
Giglio V, Varelaaramburu S, Travaglini L, Fiorini F, Seeberger P H, Maggini L, de Cola L. Reshaping silica particles: mesoporous nanodiscs for bimodal delivery and improved cellular uptake. Chemical Engineering Journal, 2018, 340: 148–154
|
13 |
Yang Y, Lu Y, Abbaraju P L, Zhang J, Zhang M, Xiang G, Yu C. Multi-shelled dendritic mesoporous organosilica hollow spheres: roles of composition and architecture in cancer immunotherapy. Angewandte Chemie International Edition, 2017, 56(29): 8446–8450
|
14 |
Abbaraju P L, Meka A K, Song H, Yang Y, Jambhrunkar M, Zhang J, Xu C, Yu M, Yu C. Asymmetric silica nanoparticles with tunable headtail structures enhance hemocompatibility and maturation of immune cells. Journal of the American Chemical Society, 2017, 139(18): 6321–6328
|
15 |
Wang X, Li X, Ito A, Watanabe Y, Sogo Y, Tsuji N M, Ohno T. Stimulation of in vivo antitumor immunity with hollow mesoporous silica nanospheres. Angewandte Chemie International Edition, 2016, 55(5): 1899–1903
|
16 |
Li X, Wang X, Sogo Y, Ohno T, Onuma K, Ito A. Mesoporous silicacalcium phosphate-tuberculin purified protein derivative composites as an effective adjuvant for cancer immunotherapy. Advanced Healthcare Materials, 2013, 2(6): 863–871
|
17 |
Li W A, Lu B Y, Gu L, Choi Y, Kim J, Mooney D J. The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration. Biomaterials, 2016, 83: 249–256
|
18 |
Wang X, Li X, Yoshiyuki K, Watanabe Y, Sogo Y, Ohno T, Tsuji N M, Ito A. Comprehensive mechanism analysis of mesoporous-silica-nanoparticle-induced cancer immunotherapy. Advanced Healthcare Materials, 2016, 5(10): 1169–1176
|
19 |
An M, Li M, Xi J, Liu H. Silica nanoparticle as a lymph node targeting platform for vaccine delivery. ACS Applied Materials & Interfaces, 2017, 9(28): 23466–23475
|
20 |
Cha B G, Jeong J H, Kim J. Extra-large pore mesoporous silica nanoparticles enabling co-delivery of high amounts of protein antigen and toll-like receptor 9 agonist for enhanced cancer vaccine efficacy. ACS Central Science, 2018, 4(4): 484–492
|
21 |
Moon D S, Lee J K. Tunable synthesis of hierarchical mesoporous silica nanoparticles with radial wrinkle structure. Langmuir, 2012, 28(33): 12341–12347
|
22 |
Du X, Qiao S. Dendritic silica particles with center-radial pore channels: promising platforms for catalysis and biomedical applications. Small, 2015, 11(4): 392–413
|
23 |
Shen Z, Li Y, Wen H, Ren X, Liu J, Yang L. Investigation on the role of surfactants in bubble-algae interaction in flotation harvesting of Chlorella vulgaris. Scientific Reports, 2018, 8(1): 3303
|
24 |
Kuai R, Ochyl L J, Bahjat K S, Schwendeman A, Moon J J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nature Materials, 2016, 16(4): 489–496
|
25 |
Bowen W S, Svrivastava A K, Batra L, Barsoumian H, Shirwan H. Current challenges for cancer vaccine adjuvant development. Expert Review of Vaccines, 2018, 17(3): 207–215
|
26 |
Warrier V U, Makandar A I, Garg M, Sethi G, Kant R, Pal J K, Yuba E, Gupta R K. Engineering anti-cancer nanovaccine based on antigen cross-presentation. Bioscience Reports, 2019, 39(10): BSR20193220
|
27 |
Casaravilla C, Pittini Á, Rückerl D, Seoane P I, Jenkins S J, MacDonald A S, Ferreira A M, Allen J E, Díaz Á. Unconventional maturation of dendritic cells induced by particles from the laminated layer of larval Echinococcus granulosus. Infection and Immunity, 2014, 82(8): 3164–3176
|
28 |
Yoshida S, Gaeta I, Pacitto R, Krienke L, Alge O, Gregorka B, Swanson J A. Differential signaling during macropinocytosis in response to M-CSF and PMA in macrophages. Frontiers in Physiology, 2015, 6: 8
|
29 |
Kasai H, Inoue K, Imamura K, Yuvienco C, Montclare J K, Yamano S. Efficient siRNA delivery and gene silencing using a lipopolypeptide hybrid vector mediated by a caveolae-mediated and temperature-dependent endocytic pathway. Journal of Nanobiotechnology, 2019, 17(1): 11
|
30 |
El-Sayed A, Harashima H. Endocytosis of gene delivery vectors: from clathrin-dependent to lipid raft-mediated endocytosis. Molecular Therapy, 2013, 21(6): 1118–1130
|
31 |
Kubiak Ossowska K, Jachimska B, Al Qaraghuli M, Mulheran P A. Protein interactions with negatively charged inorganic surfaces. Current Opinion in Colloid & Interface Science, 2019, 41: 104–117
|
32 |
Slowing I, Trewyn B G, Lin V S Y. Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. Journal of the American Chemical Society, 2006, 128(46): 14792–14793
|
33 |
Latz E, Schoenemeyer A, Visintin A, Fitzgerald K A, Monks B G, Knetter C F, Lien E, Nilsen N J, Espevik T, Golenbock D T. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nature Immunology, 2004, 5(2): 190–198
|
34 |
Hjortø G M, Larsen O, Steen A, Daugvilaite V, Berg C, Fares S, Hansen M, Ali S, Rosenkilde M M. Differential CCR7 targeting in dendritic cells by three naturally occurring CC-chemokines. Frontiers in Immunology, 2016, 7: 568
|
35 |
Gerlach C, Moseman E A, Loughhead S M, Alvarez D, Zwijnenburg A J, Waanders L, Garg R, de la Torre J C, von Andrian U H. The chemokine receptor CX3CR1 defines three antigen-experienced CD8+ T cell subsets with distinct roles in immune surveillance and homeostasis. Immunity, 2016, 45(6): 1270–1284
|
36 |
Lutz M B, Schuler G. Immature, semi-mature and fully mature dendritic cells: Which signals induce tolerance or immunity? Trends in Immunology, 2002, 23(9): 445–449
|
37 |
Tugues S, Burkhard S H, Ohs I, Vrohlings M, Nussbaum K, Vom Berg J, Kulig P, Becher B. New insights into IL-12-mediated tumor suppression. Cell Death and Differentiation, 2015, 22(2): 237–246
|
38 |
Kaplanski G, Marin V, Montero Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends in Immunology, 2003, 24(1): 25–29
|
39 |
Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt D P, Pabst R, Lutz M B, Sorokin L. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity, 2005, 22(1): 19–29
|
40 |
Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annual Review of Immunology, 2004, 22(1): 745–763
|
41 |
Nimmerjahn F, Bruhns P, Horiuchi K, Ravetch J V. FcgRIV: a novel FcR with distinct IgG subclass specificity. Immunity, 2005, 23(1): 41–51
|
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