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仿生病毒样介孔硅纳米粒子提高了细胞内化效率,实现了抗原和激动剂的共递送,从而增强了肿瘤免疫治疗效果。

Biomimetic virus-like mesoporous silica nanoparticles improved cellular internalization for co-delivery of antigen and agonist to enhance Tumor immunotherapy.

机构信息

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.

School of Pharmacy, China Medical University, Shenyang, 110122, China.

出版信息

Drug Deliv. 2023 Dec;30(1):2183814. doi: 10.1080/10717544.2023.2183814.


DOI:10.1080/10717544.2023.2183814
PMID:36843529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9980018/
Abstract

Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8 T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system.

摘要

纳米载体抗原药物传递系统与免疫细胞特异性相互作用,并提供智能传递模式,以提高抗原传递效率并促进免疫进展。然而,这些纳米颗粒通常与细胞的黏附力较弱,随后细胞吸收不足,导致免疫反应失败。受病毒结构和功能的启发,通过模拟病毒的表面结构、向心-辐射状刺突结构和粗糙表面拓扑结构,制备了类似病毒的介孔硅纳米颗粒(VMSNs),并与 Toll 样受体 7/8 激动剂咪喹莫特(IMQ)和卵清蛋白(OVA)抗原共同作用。与传统的球形介孔硅纳米颗粒(MSNs)相比,VMSNs 在细胞和动物水平均表现出良好的生物相容性,具有更高的细胞入侵能力和独特的内吞途径,该途径从溶酶体中释放出来并促进抗原交叉表达。此外,VMSNs 通过激活 DCs 成熟并增加 CD8+T 细胞的比例,有效抑制了 B16-OVA 肿瘤的生长。这项工作表明,类似病毒的介孔硅纳米颗粒共同提供 OVA 和 IMQ,可以诱导强烈的肿瘤免疫反应并抑制肿瘤生长,这是由于表面刺突结构引起了强烈的细胞免疫反应,无疑为进一步优化纳米疫苗传递系统提供了良好的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/a44dc5ecd435/IDRD_A_2183814_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/8762326fb46d/IDRD_A_2183814_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/b8768a6fbdfa/IDRD_A_2183814_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/97fdbfff77ee/IDRD_A_2183814_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/7217c13e0bc9/IDRD_A_2183814_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/4b1f046155d8/IDRD_A_2183814_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/d533eeba698f/IDRD_A_2183814_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/691f986e7d72/IDRD_A_2183814_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/868fbd573190/IDRD_A_2183814_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/f87492081389/IDRD_A_2183814_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/a44dc5ecd435/IDRD_A_2183814_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/8762326fb46d/IDRD_A_2183814_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/b8768a6fbdfa/IDRD_A_2183814_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/97fdbfff77ee/IDRD_A_2183814_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/7217c13e0bc9/IDRD_A_2183814_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/4b1f046155d8/IDRD_A_2183814_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/d533eeba698f/IDRD_A_2183814_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/691f986e7d72/IDRD_A_2183814_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/868fbd573190/IDRD_A_2183814_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/f87492081389/IDRD_A_2183814_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e09/9980018/a44dc5ecd435/IDRD_A_2183814_F0009_C.jpg

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[7]
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[8]
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本文引用的文献

[1]
Rapid and ultrasensitive detection of SARS-CoV-2 spike protein based on upconversion luminescence biosensor for COVID-19 point-of-care diagnostics.

Mater Des. 2022-11

[2]
Corrigendum to "Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy" [Bioactive Mater. 16 107-119].

Bioact Mater. 2022-9-7

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Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy.

Adv Sci (Weinh). 2022-9

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Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms.

Acta Pharm Sin B. 2022-3

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ACS Appl Mater Interfaces. 2021-10-27

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Acta Biomater. 2021-12

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Local topology and bifurcation hot-spots in proteins with SARS-CoV-2 spike protein as an example.

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