Maturation of dendritic cells in vitro and immunological enhancement of mice in vivo by pachyman- and/or OVA-encapsulated poly(d,l-lactic acid) nanospheres

茯苓多糖和/或 OVA 包裹的聚(d,l-乳酸)纳米球体外促进树突状细胞成熟,并增强小鼠体内免疫力

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作者:Sisi Zheng #, Tao Qin #, Yu Lu, Yifan Huang, Li Luo, Zhenguang Liu, Ruonan Bo, Yuanliang Hu, Jiaguo Liu, Deyun Wang

Background

Poly lactide (PLA) was proved in the last years to be good for use in sustained drug delivery and as carriers for vaccine antigens. In our previous research, pachyman (PHY)-encapsulated PLA (PHYP) nanospheres were synthesized and their function of controlling drug release was demonstrated.

Conclusion

It was corroborated that PHY- and/or OVA-encapsulated PLA nanospheres elicited prominent antigen-presenting effects on BMDCs and heightened humoral and cellular immune responses compared with other formulations.

Methods

The maturation and antigen uptake of BMDCs were evaluated, both alone and with formulated antigen PHYP nanospheres, ie, ovalbumin (OVA)-loaded PHYP nanospheres, as an antigen delivery system, to investigate antigen-specific humoral and cellular immune responses.

Purpose

In order to modify the fast drug-release rate of PHY when inoculated alone, the maturation of bone marrow dendritic cells (BMDCs) in vitro and their immunological enhancement in vivo were explored using PHYP nanospheres.

Results

The results indicated that, when stimulated by PHYP, the BMDCs matured as a result of upregulated expression of co-stimulatory molecules; the mechanism was elucidated by tracing fluorescently labeled antigens in confocal laser scanning microscopy images and observing the uptake of nanospheres by transmission electron microscopy. It was further revealed that mice inoculated with OVA-PHYP had augmented antigen-specific IgG antibodies, increased cytokine secretion by splenocytes, increased splenocyte proliferation, and activation of cluster of differentiation (CD)4+ and CD8+ T cells in vivo. Elevated immune responses were produced by OVA-PHYP, possibly owing to the activation and maturation of dendritic cells (in draining lymph nodes).

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