Nanovaccines: Merits, and diverse roles in boosting antitumor immune responses

Figures & data

Table 1. Characteristics and functions of nanoparticles.

Properties of nanovaccines	Types	Effect
Size	20–50 nm	Tend to drain to the lymphatic vessels and accumulate in the lymph nodes
	50–100 nm	Internalization of NPs by DCs is greater
	＞100 nm	More likely taken up by macrophages via phagocytosis at the injection site
Shape	Sphericity	The fastest endocytosis rate, the minimal membrane-bending energy change and high efficacy for vaccine delivery
	Star	Similar behavior with the spherical ones in wrapping time and high efficacy for antigens delivery
	Cube	-
	Rod- like	-
	Disk-like	Maximal membrane-bending energy change and low endocytosis rate
Surface charge	Cation	Efficient antigen uptake, molecular activation of APCs and distinct biodistribution profiles
	Anion	-
Polarity	Hydrophilicity	Tend to form small NPs, easier to accumulate in B cells and increase immune cellular internalization
	Hydrophobicity	Trigger the formation of larger particles

Figure 1. Scheme for the antitumor immune mechanism of nanovaccine. The nanovaccine was injected subcutaneously and accumulated in draining LNs, and then enhanced DCs maturation and antigen presenting. Antigen-specific cytotoxic T cells were induced, subsequently infiltrated into tumors, and triggered tumor cells specific lysis.⁵¹ Copyright 2021 Elsevier.

Figure 2. Effect of the nanovaccines on DCs. DCs become maturation after they uptake antigens, meanwhile, the co-stimulatory molecules(cd40, CD80 and CD86) are upregulated and bind to the CD28 of T cells. Follow by the DCs present antigens to T cells and promote the infiltration of CTL into the tumor.

Figure 3. Antigen depot effect of the nanovaccines. The antigen depot is established after subcutaneous immunization of nano vaccines. The continuously released antigen from the depot stimulates the mature of DCs and boosts the infiltration ability of effector T cell.

Table 2. Preclinical study of antitumor nanovaccine.

Nanovaccines	Size	Shape	Immunological effect	Tumor
PLGA NPs^Citation63	320nm	Spherical	Increase NK cells, CD8+ and CD4+ T cell	Melanoma, lung cancer and triple-negative breast cancer
BN@HM-OVA^Citation99	94.9 nm	Spherical	Increase M1-phenotype macrophages and increment of, decrease Tregs cells	Cervical cancer and breast cancer
CS-I/J@CM NPs^Citation100	38.2 ± 6.8 nm	Spherical	Increase M1-phenotype macrophages and CD8+T cells	Glioblastoma
CCM@(PSiNPs@Au)^Citation101	243.30 ±2.82nm	Irregular	Increase CD8+T cell and memory T cell	Breast cancer
MSN-TY/OVA/CpG^Citation102	120nm	Spherical	Increase CD8+T cell	Melanoma
NanoSTING-vax^Citation103	100nm	Spherical	Increase CD8+T cell	Colon cancer and melanoma
NP-SL8^Citation80	25-50 nm	Spherical	Increase CD8+ and CD4+ T cell	T-lymphoma
OVA-NP/polyIC^Citation104	60 nm	Spherical	Increase CD8+ and CD4+ T cell	Thymoma
NP(IMDQ+OVA)^Citation105	58 nm	Irregular	Increase CD8+ and CD4+ T cell	Colon cancer and melanoma
@E7-ICG-BSA^Citation106	100 nm	Spherical	Increase CD8+T cell	Cervical cancer
iPDPA-GFLG-IMDQ(TNV)^Citation107	31.12 ± 2.37 nm	Spherical	Increase CD8+, CD4+ T cell and memory T cell	Melanoma and colon cancer
TLR7/8a-Sur^Citation108	255.0 ± 10.3 nm	Spherical	Increase CD8+T cell and memory T cell	Melanoma
Man-PLL-RT/OVA/CpG^Citation109	80.1 nm	Spherical	Increase CD8+T cell and memory T cell	Melanoma
N@P-IM150^Citation110	238.7 nm	Spherical	Increase CD8+, CD4+ T cell and memory T cell	Breast cancer
liposomal rTL(LrTL)^Citation67	95 nm	Spherical	Decrease Tregs cells and M1-phenotype macrophages, increase CD8+T cells	Melanoma, lung cancer and colon cancer
NVs^cp Citation111	80 nm	Spherical	Increase CD8+ and CD4+ T cell, decrease Tregs cells	Melanoma
CaBPs/OVA^Citation51	50 nm	Spherical	Increase CD8+, CD4+ T cell and memory T cell	Melanoma
Mal-NPs^Citation112	60 nm	Spherical	Increase CD8+, CD4+ T cell and memory T cell	Melanoma, and colon cancer
PCNPs^Citation91	175 nm	Spherical	Increase CD8+, CD4+ T cell and memory T cell	Colon cancer

Qin M, Li M, Song G, Yang C, Wu P, Dai W, Zhang H, Wang X, Wang Y, Zhou D, et al. Boosting innate and adaptive antitumor immunity via a biocompatible and carrier-free nanovaccine engineered by the bisphosphonates-metal coordination[J]. Nano Today. 2021:37(15):158–170.

 Web of Science ®Google Scholar

Ma L, Diao L, Peng Z, Jia Y, Xie H, Li B, Ma J, Zhang M, Cheng L, Ding D, et al. Immunotherapy and prevention of cancer by nanovaccines loaded with whole-cell components of tumor tissues or cells[J]. Adv Mater. 2021;33(43):e2104849. doi:10.1002/adma.202104849.

 PubMed Web of Science ®Google Scholar

Xie X, Feng Y, Zhang H, Su Q, Song T, Yang G, Li N, Wei X, Li T, Qin X, et al. Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy[J]. Bioact Mater. 2022;16:107–119. doi:10.1016/j.bioactmat.2022.03.008.

 PubMed Web of Science ®Google Scholar

Wang T, Zhang H, Qiu W, Han Y, Liu H, Li Z. Biomimetic nanoparticles directly remodel immunosuppressive microenvironment for boosting glioblastoma immunotherapy[J]. Bioact Mater. 2022;16:418–432. doi:10.1016/j.bioactmat.2021.12.029.

 PubMed Web of Science ®Google Scholar

Li J, Huang D, Cheng R, Figueiredo P, Fontana F, Correia A, Wang S, Liu Z, Kemell M, Torrieri G, et al. Multifunctional biomimetic nanovaccines based on photothermal and weak-immunostimulatory nanoparticulate cores for the immunotherapy of solid tumors[J]. Adv Mater. 2022;34(9):e2108012. doi:10.1002/adma.202108012.

 PubMed Web of Science ®Google Scholar

Liu Y, Yao L, Cao W, Liu Y, Zhai W, Wu Y, Wang B, Gou S, Qin Y, Qi Y, et al. Dendritic cell targeting peptide-based nanovaccines for enhanced cancer immunotherapy[J]. ACS Appl Bio Mater. 2019;2(3):1241–1254. doi:10.1021/acsabm.8b00811.

 PubMedGoogle Scholar

Shae D, Baljon JJ, Wehbe M, Christov PP, Becker KW, Kumar A, Suryadevara N, Carson CS, Palmer CR, Knight FC, et al. Co-delivery of peptide neoantigens and stimulator of interferon genes agonists enhances response to cancer vaccines[J]. ACS Nano. 2020;14(8):9904–9916. doi:10.1021/acsnano.0c02765.

 PubMed Web of Science ®Google Scholar

Pan C, Wu J, Qing S, Zhang X, Zhang L, Yue H, Zeng M, Wang B, Yuan Z, Qiu Y, et al. Biosynthesis of self-assembled proteinaceous nanoparticles for vaccination[J]. Adv Mater. 2020;32(42):e2002940. doi:10.1002/adma.202002940.

 PubMed Web of Science ®Google Scholar

Carson CS, Becker KW, Garland KM, Pagendarm HM, Stone PT, Arora K, Wang-Bishop L, Baljon JJ, Cruz LD, Joyce S, et al. A nanovaccine for enhancing cellular immunity via cytosolic co-delivery of antigen and polyIC RNA[J]. J Control Release. 2022;345:354–370. doi:10.1016/j.jconrel.2022.03.020.

 PubMed Web of Science ®Google Scholar

Stickdorn J, Stein L, Arnold-Schild D, Hahlbrock J, Medina-Montano C, Bartneck J, Ziß T, Montermann E, Kappel C, Hobernik D, et al. Systemically administered TLR7/8 agonist and antigen-conjugated nanogels govern immune responses against tumors[J]. ACS Nano. 2022;16(3):4426–4443. doi:10.1021/acsnano.1c10709.

 PubMed Web of Science ®Google Scholar

Zhang L, Wang K, Huang Y, Zhang H, Zhou L, Li A, Sun Y. Photosensitizer-induced HPV16 E7 nanovaccines for cervical cancer immunotherapy[J]. Biomaterials. 2022;282:121411. doi:10.1016/j.biomaterials.2022.121411.

 PubMed Web of Science ®Google Scholar

Xia H, Qin M, Wang Z, Wang Y, Chen B, Wan F, Tang M, Pan X, Yang Y, Liu J, et al. A pH-/enzyme-responsive nanoparticle selectively targets endosomal toll-like receptors to potentiate robust cancer vaccination[J]. Nano Lett. 2022;22(7):2978–2987. doi:10.1021/acs.nanolett.2c00185.

 PubMed Web of Science ®Google Scholar

Song H, Su Q, Shi W, Huang P, Zhang C, Zhang C, Liu Q, Wang W. Antigen epitope-TLR7/8a conjugate as self-assembled carrier-free nanovaccine for personalized immunotherapy[J]. Acta Biomater. 2022;141:398–407. doi:10.1016/j.actbio.2022.01.004.

 PubMed Web of Science ®Google Scholar

Chen J, Fang H, Hu Y, Wu J, Zhang S, Feng Y, Lin L, Tian H, Chen X. Combining mannose receptor mediated nanovaccines and gene regulated PD-L1 blockade for boosting cancer immunotherapy[J]. Bioact Mater. 2022;7:167–180. doi:10.1016/j.bioactmat.2021.05.036.

 PubMed Web of Science ®Google Scholar

Xiong X, Zhao J, Pan J, Liu C, Guo X, Zhou S. Personalized nanovaccine coated with calcinetin-expressed cancer cell membrane antigen for cancer immunotherapy[J]. Nano Lett. 2021;21(19):8418–8425. doi:10.1021/acs.nanolett.1c03004.

 PubMed Web of Science ®Google Scholar

Tang Y, Fan W, Chen G, Zhang M, Tang X, Wang H, Zhao P, Xu Q, Wu Z, Lin X, et al. Recombinant cancer nanovaccine for targeting tumor-associated macrophage and remodeling tumor microenvironment[J]. Nano Today. 2021:40(18):159–163.

 Web of Science ®Google Scholar

Su R, Chong G, Dong H, Gu J, Zang J, He R, Sun J, Zhang T, Zhao Y, Zheng X, et al. Nanovaccine biomineralization for cancer immunotherapy: a NADPH oxidase-inspired strategy for improving antigen cross-presentation via lipid peroxidation[J]. Biomaterials. 2021;277:121089. doi:10.1016/j.biomaterials.2021.121089.

 PubMed Web of Science ®Google Scholar

Luo Z, He T, Liu P, Yi Z, Zhu S, Liang X, Kang E, Gong C, Liu X. Self-Adjuvanted Molecular Activator (SeaMac) nanovaccines promote cancer immunotherapy[J]. Adv Healthc Mater. 2021;10(7):e2002080. doi:10.1002/adhm.202002080.

 PubMed Web of Science ®Google Scholar

Liang Z, Cui X, Yang L, Hu Q, Li D, Zhang X, Han L, Shi S, Shen Y, Zhao W, et al. Co-Assembled nanocomplexes of peptide neoantigen Adpgk and Toll-like receptor 9 agonist CpG ODN for efficient colorectal cancer immunotherapy[J]. Int J Pharm. 2021;608:121091. doi:10.1016/j.ijpharm.2021.121091.

 PubMedGoogle Scholar