功能化壳聚糖基复合纳米颗粒作为鼻内给药疫苗佐剂增强对粘膜的免疫反应,ACS Applied Materials & Interfaces

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功能化壳聚糖基复合纳米颗粒作为鼻内给药疫苗佐剂增强对粘膜的免疫反应
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-11-16 , DOI: 10.1021/acsami.2c17627
Yuhong Lin ₁ , Beini Sun ₂ , Zheng Jin ₁ , Kai Zhao ₁

Affiliation

用于疫苗递送的鼻腔给药是一种新型的非侵入性疫苗给药方法，可以诱导局部或全身免疫反应并克服传统注射给药带来的缺点。然而，仍然迫切需要具有缓释能力和增强粘膜部位免疫作用的粘膜疫苗和佐剂递送系统。在这项工作中，N -2-羟丙基三甲基氯化铵壳聚糖/ N , O采用离子交联法制备了-羧甲基壳聚糖纳米粒 (N-2-HACC/CMCS NPs)，具有优异的粘膜吸收性、高载药量和增强的免疫反应。为了评估 N-2-HACC/CMCS NPs 作为疫苗佐剂的潜在能力以及诱导增强的粘膜和全身免疫反应的分子机制，牛血清白蛋白 (BSA) 被用作通用模型抗原并加载到N-2-HACC/CMCS NPs 制备载有 BSA 的 N-2-HACC/CMCS 佐剂疫苗 (N-2-HACC/CMCS/BSA NPs)。充分证明具有良好生物稳定性和粘膜吸收的N-2-HACC/CMCS/BSA NPs可有效促进淋巴细胞增殖和相关促炎因子的分泌，从而刺激特异性粘膜和全身免疫反应.

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Enhanced Immune Responses to Mucosa by Functionalized Chitosan-Based Composite Nanoparticles as a Vaccine Adjuvant for Intranasal Delivery

Nasal administration for vaccine delivery is a novel non-invasive vaccine administration approach that can induce local or systemic immune responses and overcome the disadvantages caused by traditional injectable administration. However, mucosal vaccine and adjuvant delivery systems with sustained-release ability and enhanced immune effects at mucosal sites have still been highly demanded. In this work, N-2-hydroxypropyl trimethyl ammonium chloride chitosan/N,O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with excellent mucosal absorption, high drug loading capacity, and enhanced immune responses were prepared by the ionic cross-linking method. To evaluate the potential capacity of the N-2-HACC/CMCS NPs as a vaccine adjuvant and the molecular mechanism for the induction of enhanced mucosal and systemic immune responses, bovine serum albumin (BSA) was employed as a general model antigen and loaded into the N-2-HACC/CMCS NPs to prepare a BSA-loaded N-2-HACC/CMCS adjuvant vaccine (N-2-HACC/CMCS/BSA NPs). It was well demonstrated that the N-2-HACC/CMCS/BSA NPs with great biostability and mucosal absorption could effectively promote the proliferation of lymphocytes and the secretion of related pro-inflammatory factors, resulting in the stimulation of specific mucosal and systemic immune responses. This study revealed that the chitosan-based nano-delivery system can act as the mucosal vaccine adjuvant and possesses great promise in viral infectious diseases and immunization therapy.

更新日期：2022-11-16

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