A Promising Self-nanoemulsifying Adjuvant with Plant-derived Saponin D Boosts Immune Response and Exerts an Anti-tumor Effect

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jul 7

PMID 37415983

Authors

Xing Luo

Zhen Song

Xiaogqiang Zeng

Yan Ye

Hailin Zheng

Dingyi Cai

Qingpeng Yuan

Haibo Li

Yanan Tong

Dongshui Lu

Yuheng Liu

Hao Zeng

Yun Yang

Hongwu Sun

Quanming Zou

Affiliations

Soon will be listed here.

Abstract

Objectives: The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression.

Methods: In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by assay.

Results: This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity and , and delayed antigen release . The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1β andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice.

Conclusions: These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.

Citing Articles

Development of semisynthetic saponin immunostimulants.

Bai D, Kim H, Wang P Med Chem Res. 2024; 33(8):1292-1306.

PMID: 39132259 PMC: 11315725. DOI: 10.1007/s00044-024-03227-x.

References

Zhang S, Liu Y, Zhou J, Wang J, Jin G, Wang X . Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects. Int J Mol Sci. 2022; 23(23). PMC: 9741412. DOI: 10.3390/ijms232315130. View

Dadaglio G, Fayolle C, Oberkampf M, Tang A, Rudilla F, Couillin I . IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 T-cell responses. Oncoimmunology. 2020; 9(1):1758606. PMC: 7458594. DOI: 10.1080/2162402X.2020.1758606. View

Ghaemi A, Roshani Asl P, Zargaran H, Ahmadi D, Hashimi A, Abdolalipour E . Recombinant COVID-19 vaccine based on recombinant RBD/Nucleoprotein and saponin adjuvant induces long-lasting neutralizing antibodies and cellular immunity. Front Immunol. 2022; 13:974364. PMC: 9494508. DOI: 10.3389/fimmu.2022.974364. View

Ahmed O, El-Bassossy H, El-Sayed H, Abd El-Hay S . Rp-HPLC Determination of Quercetin in a Novel D-α-Tocopherol Polyethylene Glycol 1000 Succinate Based SNEDDS Formulation: Pharmacokinetics in Rat Plasma. Molecules. 2021; 26(5). PMC: 7961457. DOI: 10.3390/molecules26051435. View

Heo M, Cho M, Lim Y . Polymer nanoparticles for enhanced immune response: combined delivery of tumor antigen and small interference RNA for immunosuppressive gene to dendritic cells. Acta Biomater. 2014; 10(5):2169-76. DOI: 10.1016/j.actbio.2013.12.050. View

Silva M, Kato Y, Melo M, Phung I, Freeman B, Li Z . A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity. Sci Immunol. 2021; 6(66):eabf1152. PMC: 8763571. DOI: 10.1126/sciimmunol.abf1152. View

Liu H, Moynihan K, Zheng Y, Szeto G, Li A, Huang B . Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 2014; 507(7493):519-22. PMC: 4069155. DOI: 10.1038/nature12978. View

Chen Q, Chen M, Liu Z . Local biomaterials-assisted cancer immunotherapy to trigger systemic antitumor responses. Chem Soc Rev. 2019; 48(22):5506-5526. DOI: 10.1039/c9cs00271e. View

Bender E . Cancer immunotherapy. Nature. 2020; 552(7685):S61. DOI: 10.1038/d41586-017-08699-z. View

10.

Tong Y, Yang L, Yang Y, Song Z, Peng L, Gao J . An immunopotentiator, ophiopogonin D, encapsulated in a nanoemulsion as a robust adjuvant to improve vaccine efficacy. Acta Biomater. 2018; 77:255-267. DOI: 10.1016/j.actbio.2018.07.034. View

11.

Gao A, Hu X, Saeed M, Chen B, Li Y, Yu H . Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy. Acta Pharmacol Sin. 2019; 40(9):1129-1137. PMC: 6786406. DOI: 10.1038/s41401-019-0281-1. View

12.

Kuai R, Ochyl L, Bahjat K, Schwendeman A, Moon J . Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater. 2016; 16(4):489-496. PMC: 5374005. DOI: 10.1038/nmat4822. View

13.

Batool A, Arshad R, Razzaq S, Nousheen K, Kiani M, Shahnaz G . Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer. Int J Biol Macromol. 2020; 152:503-515. DOI: 10.1016/j.ijbiomac.2020.02.275. View

14.

Purwada A, Roy K, Singh A . Engineering vaccines and niches for immune modulation. Acta Biomater. 2013; 10(4):1728-40. DOI: 10.1016/j.actbio.2013.12.036. View

15.

Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G . Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2007; 8(1):59-73. DOI: 10.1038/nri2216. View

16.

Cai D, Zhang Z, Feng Z, Song J, Zeng X, Tu Y . A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection. Biomater Adv. 2022; 140:213029. DOI: 10.1016/j.bioadv.2022.213029. View

17.

Huang P, Wang X, Liang X, Yang J, Zhang C, Kong D . Nano-, micro-, and macroscale drug delivery systems for cancer immunotherapy. Acta Biomater. 2018; 85:1-26. DOI: 10.1016/j.actbio.2018.12.028. View

18.

Mochizuki S, Morishita H, Kobiyama K, Aoshi T, Ishii K, Sakurai K . Immunization with antigenic peptides complexed with β-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs. J Control Release. 2015; 220(Pt A):495-502. DOI: 10.1016/j.jconrel.2015.11.008. View

19.

Saxena M, van der Burg S, Melief C, Bhardwaj N . Therapeutic cancer vaccines. Nat Rev Cancer. 2021; 21(6):360-378. DOI: 10.1038/s41568-021-00346-0. View

20.

ODonnell J, Teng M, Smyth M . Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2018; 16(3):151-167. DOI: 10.1038/s41571-018-0142-8. View