Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery
Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery
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DOI：
10.1039/d1bm01985f
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发表时间：
2022-01-26
影响因子：
6.6
通讯作者：
Ohya, Yuichi
中科院分区：
文献类型：
--
作者：
Suzuki, Kengo;Yoshizaki, Yuta;Ohya, Yuichi
为建立有效的鼻腔疫苗，研制了透明质酸(HA)包被的可生物降解聚合物胶束作为纳米粒疫苗递送系统。我们以前报道过通过将聚(L-赖氨酸)-b-聚乳酸(PLYS(+)-b-PLA)胶束与HA形成多离子络合物(PIC)来制备HA包衣胶束。HA包被的胶束在HA受体表达细胞中表现出特异性的蓄积，在稀释的血液条件下具有极高的胶体稳定性。在本研究中，模型抗原卵清蛋白(OVA)和含有CG基序的佐剂寡核苷酸(CpG-DNA)通过静电相互作用有效地负载到HA包被的胶束中。HA包被的胶束可将OVA和CpG-DNA送入小鼠骨髓来源的树突状细胞(BMDCs)，并导致BMDCs中编码干扰素-γ和IL-4的mRNA表达上调。此外，HA包被的胶束增强了BMDCs上主要组织相容性复合体(MHC)II类的表达。我们研究了HA包衣胶束鼻腔给药后的免疫应答。与对照(羧甲基葡聚糖包被)胶束相比，HA包被的胶束诱导血液中的OVA特异性免疫球蛋白和鼻腔冲洗液中的OVA特异性IgA更高。这些结果表明，透明质酸包被的胶束有效地将抗原和佐剂输送到粘膜驻留的免疫细胞。因此，羟基磷灰石包衣胶束是研制抗传染病鼻腔疫苗的良好平台。
Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(l-lysine)-b-polylactide (PLys(+)-b-PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG-DNA) were efficiently loaded in HA-coated micelles via electrostatic interactions. HA-coated micelles delivered OVA and CpG-DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in the upregulation of mRNA encoding IFN-gamma and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases.