Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery--颗粒学报PARTICUOLOGY

Xu, R., Dong, Y., Zhang, Y., Wang, X., Zhang, C., & Jiang, Y. (2022). Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery. Particuology, 60, 77-89. https://doi.org/10.1016/j.partic.2021.02.007

Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery

Rong Xu ^{a 1}, Ying Dong ^{b 1}, Yajing Zhang^c^*, Xiaoli Wang ^a *, Chuangnian Zhang ^a, Yanjun Jiang ^b

a Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
b School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, 300130, China
c NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China

10.1016/j.partic.2021.02.007

Volume 60, January 2022, Pages 77-89

Received 28 September 2020, Revised 12 January 2021, Accepted 3 February 2021, Available online 31 March 2021, Version of Record 23 October 2021.

E-mail: lianyajing@163.com; wangxl@bme.pumc.edu.cn

Highlights

• A microvaccine with SiO₂ nanoparticles in CaCO₃ microparticles was constructed.

• Antigen was conjugated with SiO₂, then SiO₂ and CpG were co-encapsulated into CaCO₃.

• Vaccine was internalized via micropinocytosis and improved antigen/adjuvant uptake.

• Antigen lysosomal escape was observed, and DCs pulsed by vaccine were fully mature.

• The vaccine had good biocompatibility and protected antigens from rapid degradation.

Abstract

A microscale vaccine containing SiO₂ nanoparticles loaded in CaCO₃ microparticles was constructed using the co-precipitation method. The antigen ovalbumin (OVA) was covalently conjugated with SiO₂ nanoparticles, and these nanoparticles and CpG were co-encapsulated into CaCO₃ microparticles, generating a vaccine with a size of approximately 5.2 μm. Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), elemental mapping, and Fourier transform infrared (FTIR) analyses confirmed the successful preparation of the microscale vaccine; the vaccine had good storage stability without sustained antigen release, and negligible cytotoxicity to dendritic cells (DCs) and macrophages. Compared to SiO₂ nanoparticles, the microscale vaccine can significantly improve antigen/adjuvant uptake. DCs internalized the entire microscale vaccine into lysosomes via macropinocytosis, and an increase in antigen endo/lysosomal escape was observed by confocal laser scanning microscopy (CLSM). Specifically, DCs pulsed with the vaccine were fully mature, expressing high levels of costimulatory molecules (CD40, CD80, and CD86), MHC II, and MHC I and secreting high levels of proinflammatory cytokines (IL-12, TNF-α, IL-1β, and IL-6). In addition, the vaccine had good in vivo biocompatibility, could protect the antigen from rapid degradation, and increased the retention time in lymph nodes. SiO₂ nanoparticles-in-CaCO₃ microparticles were an excellent carrier for antigen and adjuvant delivery. Hopefully, this study can provide some information on the design of microscale carriers for vaccine delivery systems.

Graphical abstract

Keywords

Antigen delivery; Cross-presentation; Microparticle; Silica nanoparticle; Bone marrow dendritic cell

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