pH-Sensitive branched β-glucan-modified liposomes for activation of antigen presenting cells and induction of antitumor immunity,Journal of Materials Chemistry B

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pH-Sensitive branched β-glucan-modified liposomes for activation of antigen presenting cells and induction of antitumor immunity
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2021-09-02 , DOI: 10.1039/d1tb00786f
Shin Yanagihara ₁ , Nozomi Kasho ₁ , Koichi Sasaki ₁ , Naoto Shironaka ₁ , Yukiya Kitayama ₁ , Eiji Yuba ₁ , Atsushi Harada ₁

Affiliation

Induction of cellular immunity is important for effective cancer immunotherapy. Although various antigen carriers for cancer immunotherapy have been developed to date, balancing efficient antigen delivery to antigen presenting cells (APCs) and their activation via innate immune receptors, both of which are crucially important for the induction of strong cellular immunity, remains challenging. For this study, branched β-glucan was selected as an intrinsically immunity-stimulating and biocompatible material. It was engineered to develop multifunctional liposomal cancer vaccines capable of efficient interactions with APCs and subsequent activation of the cells. Hydroxy groups of branched β-glucan (Aquaβ) were modified with 3-methylglutaric acid ester and decyl groups, respectively, to provide pH-sensitivity and anchoring capability to the liposomal membrane. The modification efficiency of Aquaβ derivatives to the liposomes was significantly high compared with linear β-glucan (curdlan) derivatives. Aquaβ derivative-modified liposomes released their contents in response to weakly acidic pH. As a model antigenic protein, ovalbumin (OVA)-loaded liposomes modified with Aquaβ derivatives interacted efficiently with dendritic cells, and induced inflammatory cytokine secretion from the cells. Subcutaneous administration of Aquaβ derivative-modified liposomes suppressed the growth of the E.G7-OVA tumor significantly compared with curdlan derivative-modified liposomes. Aquaβ derivative-modified liposomes induced the increase of CD8⁺ T cells, and polarized macrophages to the antitumor M1-phenotype within the tumor microenvironment. Therefore, pH-sensitive Aquaβ derivatives can be promising materials for liposomal antigen delivery systems to induce antitumor immune responses efficiently.

中文翻译：

pH敏感的支链β-葡聚糖修饰脂质体用于激活抗原呈递细胞和诱导抗肿瘤免疫

细胞免疫的诱导对于有效的癌症免疫治疗很重要。尽管迄今为止已经开发出各种用于癌症免疫治疗的抗原载体，但平衡了向抗原呈递细胞 (APC) 的有效抗原递送及其通过先天免疫受体对于诱导强大的细胞免疫至关重要，但仍然具有挑战性。在本研究中，选择支链 β-葡聚糖作为一种内在的免疫刺激和生物相容性材料。它被设计用于开发能够与 APC 有效相互作用并随后激活细胞的多功能脂质体癌症疫苗。支链 β-葡聚糖 (Aquaβ) 的羟基分别用 3-甲基戊二酸酯和癸基修饰，以提供对脂质体膜的 pH 敏感性和锚定能力。与线性β-葡聚糖（凝乳多糖）衍生物相比，Aquaβ衍生物对脂质体的修饰效率显着提高。Aquaβ 衍生物修饰的脂质体响应弱酸性 pH 释放其内容物。作为模型抗原蛋白，用 Aquaβ 衍生物修饰的载有卵清蛋白 (OVA) 的脂质体与树突状细胞有效相互作用，并诱导细胞分泌炎性细胞因子。与 curdlan 衍生物修饰的脂质体相比，Aquaβ 衍生物修饰的脂质体的皮下给药显着抑制了 E.G7-OVA 肿瘤的生长。Aquaβ衍生物修饰的脂质体诱导CD8的增加⁺ T 细胞和极化巨噬细胞对肿瘤微环境中的抗肿瘤 M1 表型。因此，pH敏感的Aquaβ衍生物可以成为脂质体抗原递送系统有效诱导抗肿瘤免疫反应的有前景的材料。

更新日期：2021-09-22

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