Citation: Zeyu XU, Anlei DANG, Bihua DENG, Xiaoxin ZUO, Yu LU, Ping YANG, Wenzhu YIN. Evaluation of the efficacy of graphene oxide quantum dots as an ovalbumin delivery platform and adjuvant for immune enhancement[J]. Chinese Journal of Inorganic Chemistry, ;2024, 40(6): 1065-1078. doi: 10.11862/CJIC.20240099 shu

Evaluation of the efficacy of graphene oxide quantum dots as an ovalbumin delivery platform and adjuvant for immune enhancement

Zeyu XU ^{1, 2, 3} ,
Anlei DANG ^{1, 2, 3} ,
Bihua DENG ^{1, 2} ,
Xiaoxin ZUO ^{1, 2} ,
Yu LU ^{1, 2, 3} ,
Ping YANG ^3,, ,
Wenzhu YIN ^{1, 2,,}

1.
Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China
2.
Guotai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, Jiangsu 225300, China
3.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Corresponding author: Ping YANG, yangping@njau.edu.cn Wenzhu YIN, m18805157895@163.com
Received Date: 27 March 2024
Revised Date: 28 April 2024

Figures(8)

The improved Hummers method was used to obtain GOQDs from flake graphite, which contained rich hydroxyl and carboxyl groups. With the as-fabricated GOQDs in hand, we constructed a GOQDs/OVA nano-vaccine using chicken ovalbumin (OVA) as a model antigen to evaluate the immune efficacy and safety. Results showed that GOQDs/OVA nano-vaccine had high water dispersibility and stability with a diameter of around 5 nm for 30 d. The maximum loading capacity of GOQDs for OVA was about 500 mg·g^-1, and release rates of OVA were 74.65% and 56.93% in pH 5.5 and 7.4 after 24 h, respectively, displaying pH stimulus responsive release merits. With the concentration of GOQDs below 500 μg·mL^-1, the biosecurity of GOQDs indicated that they were not causing hemolysis, cell damage, and pathological changes in important tissues. After immunization, GOQDs/OVA nano-vaccines could excite the high levels of immunoglobulin G (IgG), immunoglobulin G1 (IgG1), and immunoglobulin G2a (IgG2a) antibodies and improve secretions of interleukin-1β (IL-1β), interleukin-4 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), compared with the group of OVA alone. Meanwhile, GOQDs promoted an increase in the percentage of CD4⁺ and CD8⁺ T lymphocytes in the spleen.
- graphene oxide,
- quantum dot,
- adjuvant,
- adsorption,
- antibody
1. [1]
  Sun B N, Yu S, Zhao D Y, Guo S H, Wang X H, Zhao K. Polysaccharides as vaccine adjuvants[J]. Vaccine, 2018,36(35):5226-5234. doi: 10.1016/j.vaccine.2018.07.040
2. [2]
  HAN B, TANG S Q, ZHU D W, LI H L, FENG Y L, SUN C F, XU Y N, LENG H Y, WANG Y T, ZHANG Y M, TAI X C, ZHANG Y. Research progress of novel vaccine adjuvants[J]. China Animal Husbandry & Veterinary Medicine, 2023,50(6):2460-2467.
3. [3]
  Huang S M, Li B W, Ashraf U, Li Q, Lu X C, Gao X C, Cui M, Imran M, Ye J, Cao F F, Gu J J, Cao S B. Quaternized cationic carbon dots as antigen delivery systems for improving humoral and cellular immune responses[J]. ACS Appl. Nano Mater., 2020,3(9):9449-9461. doi: 10.1021/acsanm.0c02062
4. [4]
  Du G S, Qin M, Sun X. Recent progress in application of nanovaccines for enhancing mucosal immune responses[J]. Acta Pharm. Sin. B, 2023,13(6):2334-2345. doi: 10.1016/j.apsb.2022.08.010
5. [5]
  Li S X, Bennett Z T, Sumer B D, Gao J M. Nano-immune-engineering approaches to advance cancer immunotherapy: Lessons from ultra-pH-sensitive nanoparticles[J]. Acc. Chem. Res., 2020,53(11):2546-2557. doi: 10.1021/acs.accounts.0c00475
6. [6]
  Yan H, Lin G B, Liu Z Y, Gu F, Zhang Y. Nano-adjuvants and immune agonists promote antitumor immunity of peptide amphiphiles[J]. Acta Biomater., 2023,161:213-225. doi: 10.1016/j.actbio.2023.02.034
7. [7]
  Mao L Z, Ma P Q, Luo X, Cheng H W, Wang Z X, Ye E, Loh X J, Wu Y L, Li Z. Stimuli-responsive polymeric nanovaccines toward next-generation immunotherapy[J]. ACS Nano, 2023,17(11):9826-9849. doi: 10.1021/acsnano.3c02273
8. [8]
  Wang X L, Gao X L, Wang L X, Lin J H, Liu Y. Advances of nanotechnology toward vaccine development against animal infectious diseases[J]. Adv. Funct. Mater., 2023,33(46)2305061. doi: 10.1002/adfm.202305061
9. [9]
  WANG H J, YIN G. Orange emission graphene oxide quantum dots: A one-pot strategy for highly efficient fabrication and application in the imaging of pH in living cells[J]. Chinese J. Inorg. Chem, 2023,39(7):1338-1448.
10. [10]
  Li S, Guo Z, Zeng G D, Zhang Y, Xue W, Liu Z H. Polyethylenimine-modified fluorescent carbon dots as vaccine delivery system for intranasal immunization[J]. ACS Biomater. Sci. Eng., 2018,4(1):142-150. doi: 10.1021/acsbiomaterials.7b00370
11. [11]
  Zhao L H, Shu M Y, Chen H L, Shi K L, Li Z Y. Preparation of graphene oxide-stabilized pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against chlamydia trachomatis infection[J]. Front. Immunol., 2023,141148253. doi: 10.3389/fimmu.2023.1148253
12. [12]
  Huang S Y, Li Y Y, Zhang S, Chen Y M, Su W Q, Sanchez D J, Mai J D H, Zhi X, Chen H J, Ding X T. A self-assembled graphene oxide adjuvant induces both enhanced humoral and cellular immune responses in influenza vaccine[J]. J. Control Release, 2024,365:716-728. doi: 10.1016/j.jconrel.2023.11.047
13. [13]
  Qin Y R, Zhou Z W, Pan S T, He Z X, Zhang X J, Qiu J X, Duan W, Yang T X, Zhou S F. Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated thp-1 macrophages[J]. Toxicology, 2015,327:62-76. doi: 10.1016/j.tox.2014.10.011
14. [14]
  Du T, Liang J G, Dong N, Liu L, Fang L R, Xiao S B, Han H Y. Carbon dots as inhibitors of virus by activation of type Ⅰ interferon response[J]. Carbon, 2016,110:278-285. doi: 10.1016/j.carbon.2016.09.032
15. [15]
  Xiao Y Q, Pang Y X, Yan Y X, Qian P, Zhao H T, Manickam S, Wu T, Pang C H. Synthesis and functionalization of graphene materials for biomedical applications: Recent advances, challenges, and perspectives[J]. Adv. Sci., 2023,10(9)e2205292. doi: 10.1002/advs.202205292
16. [16]
  Vakili B, Karami-Darehnaranji M, Mirzaei E, Hosseini F, Nezafat N. Graphene oxide as novel vaccine adjuvant[J]. Int. Immunopharmacol., 2023,125111062. doi: 10.1016/j.intimp.2023.111062
17. [17]
  Hummers W S, Offeman R E. Preparation of graphitic oxide[J]. J. Am. Chem. Soc., 1958,80(6)1339. doi: 10.1021/ja01539a017
18. [18]
  Liu H H, Xu A, Feng Z J, Long D, Chen X Y, Lu M. pH-dependent fluorescent quenching of graphene oxide quantum dots: Towards hydroxyl[J]. Mater. Sci. Eng. B-Adv. Funct. Solid-State Mater., 2020,260114627. doi: 10.1016/j.mseb.2020.114627
19. [19]
  Marcano D C, Kosynkin D V, Berlin J M, Sinitskii A, Sun Z Z, Slesarev A, Alemany L B, Lu W, Tour J M. Improved synthesis of graphene oxide[J]. ACS Nano, 2010,4(8):4806-4014. doi: 10.1021/nn1006368
20. [20]
  Yang Y X, Huo D Q, Wu H X, Wang X F, Yang J S, Bian M H, Ma Y, Hou C J. N, P-doped carbon quantum dots as a fluorescent sensing platform for carbendazim detection based on fluorescence resonance energy transfer[J]. Sens. Actuator B-Chem., 2018,274:296-303. doi: 10.1016/j.snb.2018.07.130
21. [21]
  Liu Y J, Ying D Y, Cai Y X, Le X Y. Improved antioxidant activity and physicochemical properties of curcumin by adding ovalbumin and its structural characterization[J]. Food Hydrocolloids, 2017,72:304-311. doi: 10.1016/j.foodhyd.2017.06.007
22. [22]
  Cui L, Ren X, Wang J, Sun M T. Synthesis of homogeneous carbon quantum dots by ultrafast dualbeam pulsed laser ablation for bioimaging[J]. Mater. Today Nano, 2020,12100091. doi: 10.1016/j.mtnano.2020.100091
23. [23]
  Hafermann M J, Namdar R, Seibold G E, Lee R. Effect of intravenous ondansetron on qt interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study[J]. Drug Healthc. Patient Saf., 2011,3:53-58.
24. [24]
  Colby L A, Quenee L E, Zitzow L A. Considerations for infectious disease research studies using animals[J]. Comparative Med., 2017,67(3):222-231.
25. [25]
  Tang S H, Huang Y Y, Zheng J. Salivary excretion of renal-clearable silver nanoparticles[J]. Angew. Chem. Int. Ed., 2020,59(45):19894-19898. doi: 10.1002/anie.202008416
26. [26]
  Poon W, Zhang Y N, Ouyang B, Kingston B R, Wu J L Y, Wilhelm S, Chan W C W. Elimination pathways of nanoparticles[J]. ACS Nano, 2019,13(5):5785-5798. doi: 10.1021/acsnano.9b01383
27. [27]
  LI P J, YAO F G. Effect of ginseng ling yangxin tang on blood biochemical and cardiac function indices in patients with chronic heart faliure and evaluation of the safety of drug administrstion[J]. Clinical Research, 2023,31(10):111-114.
28. [28]
  Boehm O, Zur B, Koch A, Tran N, Freyenhagen R, Hartmann M, Zacharowski K. Clinical chemistry reference database for Wistar rats and C57/Bl6 mice[J]. Biol. Chem., 2007,388(5):547-554. doi: 10.1515/BC.2007.061
29. [29]
  Kurapati R, Mukherjee S P, Martín C, Bepete G, Vázquez E, Pénicaud A, Fadeel B, Bianco A. Degradation of single-layer and few-layer graphene by neutrophil myeloperoxidase[J]. Angew. Chem. Int. Ed., 2018,57(36):11722-11727. doi: 10.1002/anie.201806906
30. [30]
  Zhao L, Seth A, Wibowo N, Zhao C X, Mitter N, Yu C, Middelberg A P. Nanoparticle vaccines[J]. Vaccine, 2014,32(3):327-337. doi: 10.1016/j.vaccine.2013.11.069
31. [31]
  Habib A, Anjum K M, Iqbal R, Jaffar G, Ashraf Z, Khalid M S, Taj M U, Zainab S W, Umair M, Zohaib M, Khalid T. Vaccine adjuvants: Selection criteria, mechanism of action associated with immune responses and future directions[J]. Iran. J. Immunol., 2023,20(1):1-15.
32. [32]
  Nguyen B, Tolia N H. Protein-based antigen presentation platforms for nanoparticle vaccines[J]. npj Vaccines, 2021,6(1)70.
33. [33]
  Barinov A, Galgano A, Krenn G, Tanchot C, Vasseur F, Rocha B. CD4/CD8/dendritic cell complexes in the spleen: CD8⁺T cells can directly bind CD4⁺T cells and modulate their response[J]. PLoS One, 2017,12(7)e0180644.
34. [34]
  Pondeljak N, Lugovic-mihic L. Stress-induced interaction of skin immune cells, hormones, and neurotransmitters[J]. Clin. Ther., 2020,42(5):757-770.
35. [35]
  Kalinski P, Wieckowski E, Muthuswamy R, De Jong E. Generation of stable Th1/CTL-, Th2-, and Th17-inducing human dendritic cells//Naik S H. Dendritic Cell Protocols. 2nd ed. New York: Humana Press, 2010, 595: 117-133
36. [36]
  Kilgore P B, Sha J, Andersson J A, Motin V L, Chopra A K. A new generation needle- and adjuvant-free trivalent plague vaccine utilizing adenovirus-5 nanoparticle platform[J]. npj Vaccines, 2021,6(1)21.
37. [37]
  Lam J H, Baumgarth N. Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses[J]. Nat. Commun., 2023,14(1)3979.
1. [1]
  Hui Wang , Abdelkader Labidi , Menghan Ren , Feroz Shaik , Chuanyi Wang . Recent Progress of Microstructure-Regulated g-C₃N₄ in Photocatalytic NO Conversion: The Pivotal Roles of Adsorption/Activation Sites. Acta Physico-Chimica Sinica, 2025, 41(5): 100039-0. doi: 10.1016/j.actphy.2024.100039
2. [2]
  Zhuo WANG , Junshan ZHANG , Shaoyan YANG , Lingyan ZHOU , Yedi LI , Yuanpei LAN . Preparation and photocatalytic performance of CeO₂-reduced graphene oxide by thermal decomposition. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1708-1718. doi: 10.11862/CJIC.20240067
3. [3]
  Miaomiao He , Zhiqing Ge , Qiang Zhou , Jiaqing He , Hong Gong , Lingling Li , Pingping Zhu , Wei Shao . Exploring the Fascinating Realm of Quantum Dots. University Chemistry, 2024, 39(6): 231-237. doi: 10.3866/PKU.DXHX202310040
4. [4]
  Yu SU , Xinlian FAN , Yao YIN , Lin WANG . From synthesis to application: Development and prospects of InP quantum dots. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2105-2123. doi: 10.11862/CJIC.20240126
5. [5]
  Jingke LIU , Jia CHEN , Yingchao HAN . Nano hydroxyapatite stable suspension system: Preparation and cobalt adsorption performance. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1763-1774. doi: 10.11862/CJIC.20240060
6. [6]
  Peng XU , Shasha WANG , Nannan CHEN , Ao WANG , Dongmei YU . Preparation of three-layer magnetic composite Fe₃O₄@polyacrylic acid@ZiF-8 for efficient removal of malachite green in water. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 544-554. doi: 10.11862/CJIC.20230239
7. [7]
  Jing Wang , Pingping Li , Yuehui Wang , Yifan Xiu , Bingqian Zhang , Shuwen Wang , Hongtao Gao . Treatment and Discharge Evaluation of Phosphorus-Containing Wastewater. University Chemistry, 2024, 39(5): 52-62. doi: 10.3866/PKU.DXHX202309097
8. [8]
  Guang Huang , Lei Li , Dingyi Zhang , Xingze Wang , Yugai Huang , Wenhui Liang , Zhifen Guo , Wenmei Jiao . Cobalt’s Valor, Nickel’s Foe: A Comprehensive Chemical Experiment Utilizing a Cobalt-based Imidazolate Framework for Nickel Ion Removal. University Chemistry, 2024, 39(8): 174-183. doi: 10.3866/PKU.DXHX202311051
9. [9]
  Fugui XI , Du LI , Zhourui YAN , Hui WANG , Junyu XIANG , Zhiyun DONG . Functionalized zirconium metal-organic frameworks for the removal of tetracycline from water. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 683-694. doi: 10.11862/CJIC.20240291
10. [10]
  Wei Li , Jinfan Xu , Yongjun Zhang , Ying Guan . 共价有机框架整体材料的制备及食品安全非靶向筛查应用——推荐一个仪器分析综合化学实验. University Chemistry, 2025, 40(6): 276-285. doi: 10.12461/PKU.DXHX202406013
11. [11]
  Yunting Shang , Yue Dai , Jianxin Zhang , Nan Zhu , Yan Su . Something about RGO (Reduced Graphene Oxide). University Chemistry, 2024, 39(9): 273-278. doi: 10.3866/PKU.DXHX202306050
12. [12]
  Zhihuan XU , Qing KANG , Yuzhen LONG , Qian YUAN , Cidong LIU , Xin LI , Genghuai TANG , Yuqing LIAO . Effect of graphene oxide concentration on the electrochemical properties of reduced graphene oxide/ZnS. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1329-1336. doi: 10.11862/CJIC.20230447
13. [13]
  Wenlong Wang , Wentao Hao , Lang He , Jia Qiao , Ning Li , Chaoqiu Chen , Yong Qin . Bandgap and adsorption engineering of carbon dots/TiO₂ S-scheme heterojunctions for enhanced photocatalytic CO₂ methanation. Acta Physico-Chimica Sinica, 2025, 41(9): 100116-0. doi: 10.1016/j.actphy.2025.100116
14. [14]
  Yue Zhang , Bao Li , Lixin Wu . GO-Assisted Supramolecular Framework Membrane for High-Performance Separation of Nanosized Oil-in-Water Emulsions. Acta Physico-Chimica Sinica, 2024, 40(5): 2305038-0. doi: 10.3866/PKU.WHXB202305038
15. [15]
  Shuanglin TIAN , Tinghong GAO , Yutao LIU , Qian CHEN , Quan XIE , Qingquan XIAO , Yongchao LIANG . First-principles study of adsorption of Cl₂ and CO gas molecules by transition metal-doped g-GaN. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1189-1200. doi: 10.11862/CJIC.20230482
16. [16]
  Ping ZHANG , Chenchen ZHAO , Xiaoyun CUI , Bing XIE , Yihan LIU , Haiyu LIN , Jiale ZHANG , Yu'nan CHEN . Preparation and adsorption-photocatalytic performance of ZnAl@layered double oxides. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1965-1974. doi: 10.11862/CJIC.20240014
17. [17]
  Shiqian WEI , Xinyu TIAN , Hong LIU , Maoxia CHEN , Fan TANG , Qiang FAN , Weifeng FAN , Yu HU . Oxygen reduction reaction/oxygen evolution reaction catalytic performances of different active sites on nitrogen-doped graphene loaded with iron single atoms. Chinese Journal of Inorganic Chemistry, 2025, 41(9): 1776-1788. doi: 10.11862/CJIC.20250102
18. [18]
  Jianjun Liu , Xue Yang , Chi Zhang , Xueyu Zhao , Zhiwei Zhang , Yongmei Chen , Qinghong Xu , Shao Jin . Preparation and Fluorescence Characterization of CdTe Semiconductor Quantum Dots. University Chemistry, 2024, 39(7): 307-315. doi: 10.3866/PKU.DXHX202311031
19. [19]
  Lingqi Zhang , Hairong Huang , Jialin Li , Li Ji , Yufan Pan , Meiling Ye , Cuixue Chen , Shunü Peng . 桂花碳量子点的绿色制备及科普应用方案. University Chemistry, 2025, 40(8): 298-306. doi: 10.12461/PKU.DXHX202409138
20. [20]
  Li'na ZHONG , Jingling CHEN , Qinghua ZHAO . Synthesis of multi-responsive carbon quantum dots from green carbon sources for detection of iron ions and L-ascorbic acid. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 709-718. doi: 10.11862/CJIC.20240280

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(829)
HTML views(94)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142