A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect

Liú, Dan; Liu, Jiale; Ma, Bing; Deng, Bo; Leng, Xigang; Kong, Deling; Liu, Lanxia

doi:10.1039/d0bm01333a

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…The fluorescence intensity in the MCO NVs group was 2.8- and 2.0-fold higher than those of the Free OVA and the Free MPLA/CpG ODN/OVA (Free MCO) group, respectively (Figure S5). These results indicated that MCO NVs could significantly improve the BMDCs’ uptake of antigens and adjuvants, with the mechanism mainly owing to the formation of the hollow spherical nucleic acid (SNA) nanostructure which has a great cellular entry ability. − …”

Section: Resultsmentioning

confidence: 85%

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine

et al. 2021

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Nanovaccines have emerged as promising agents for cancer immunotherapy. However, insufficient antitumor immunity caused by inefficient antigen/adjuvant loading and complicated preparation processes are the major obstacles that limit their clinical application. Herein, two adjuvants, monophosphatidyl A (MPLA) and CpG ODN, with antigens were designed into a nanovaccine to overcome the above obstacles. This nanovaccine was constructed with adjuvants (without additional materials) through facile self-assembly, which not only ensured a high loading efficacy and desirable safety but also facilitated clinical translation for convenient fabrication. More importantly, the selected adjuvants could achieve a notable immune response through synergistic activation of Toll-like receptor 4 (TLR4) and TLR9 signaling pathways, and the resulting nanovaccine remarkably inhibited the tumor growth and prolonged the survival of tumor-implanted mice. This nanovaccine system provides an effective strategy to construct vaccines for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 85%

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine

et al. 2021

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“…To further explore the pathway of R837@HM-NPs into BMDCs, we pretreated these cells with several cellular uptake inhibitors and blocked the corresponding endocytic pathway. 26 , 27 BMDCs were treated with filipin (15 μg/mL), amiloride (10 μg/mL), chlorpromazine (10 μg/mL), monensin (10 μg/mL), methyl-β-cyclodextrin (10 μg/mL), and ethylisopropylamiloride (20 μg/mL) at 37 °C for 2 h. The pretreated cells then were co-incubated with R837@HM-NPs for 4 h and untreated cells were used as a negative control. The cells were then trypsinized, centrifuged, and lysed by ultrasonication.…”

Section: Methodsmentioning

confidence: 99%

Hybrid Membrane Nanovaccines Combined with Immune Checkpoint Blockade to Enhance Cancer Immunotherapy

Zhao¹,

Xu²,

Ji³

et al. 2022

IJN

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Purpose Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues. Methods Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments. Results R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect. Conclusion These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity.

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“…The obtained nanovaccines could provide sustained and effective antigen stimulation, promote the release of some immune factors, further boost significantly anti-tumor immunity to inhibit tumor growth. 86 Moreover, there is another way to introduce CpG into tumor nanovaccines through the formation of covalent bonds between S and other atoms. For example, Zhu et al developed albumin/albumin-binding vaccines (AlbiVax) nanocomplexes that achieved high efficiency co-delivery of antigen and adjuvant CpG.…”

Section: Cpg Loaded In Nanovaccines By Covalent Bondingmentioning

confidence: 99%

CpG-Based Nanovaccines for Cancer Immunotherapy

Chen¹,

Jiang²,

Yu³

et al. 2021

IJN

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Cancer has been a serious health hazard to the people all over the world with its high incidence and horrible mortality. In recent years, tumor vaccines in immunotherapy have become a hotspot in cancer therapy due to their many practical advantages and good therapeutic potentials. Among the various vaccines, nanovaccine utilized nanoparticles (NPs) as the carrier and/or adjuvant has presented significant therapeutic effect in cancer treatment. For tumor nanovaccines, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) is a commonly used adjuvant. It has been reported that CpG ODN was the most effective immune stimulant among the currently known adjuvants. It could be recognized by toll-like receptor 9 (TLR9) to activate humoral and cellular immunity for preventing or treating cancer. In this review, the topic of CpG-based nanovaccines for cancer immunotherapy will be focused. The types and properties of different CpG will be introduced in detail first, and then some representative tumor nanovaccines will be reviewed according to the diverse loading modes of CpG, such as electrostatic adsorption, covalent bonding, hydrophilic and hydrophobic interaction, and DNA self-assembly, for summarizing the current progress of CpG-based tumor nanovaccines. Finally, the challenges and future perspectives will be discussed. It is hoped that this review will provide valuable references for the development of nanovaccines in cancer immunotherapy.

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A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect

Abstract: Biomimetic nanoparticles have potential applications in many fields for their favorable properties. Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthetized with phospholipids...

Cited by 15 publications

References 47 publications

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine

Hybrid Membrane Nanovaccines Combined with Immune Checkpoint Blockade to Enhance Cancer Immunotherapy

CpG-Based Nanovaccines for Cancer Immunotherapy

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