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Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: A new tumor-vaccine carrier for eliciting effector T cells

机译:通过两亲性γ-PGA自组装而构建的纳米颗粒可以将抗原高效地递送至抗原呈递细胞:一种新型的肿瘤疫苗载体,用于诱导效应T细胞

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摘要

Nanotechnology is a fundamental technology for designing and generating innovative carriers for biomacromolecular drugs. Biodegradable poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs, and these antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.
机译:纳米技术是设计和生成生物大分子药物创新载体的基础技术。可生物降解的基于聚(γ-谷氨酸)的纳米颗粒(γ-PGANPs)是出色的疫苗载体,能够将抗原蛋白递送至抗原呈递细胞(APC)并基于抗原特异性细胞毒性T淋巴细胞引发强力免疫反应。在小鼠中,用包裹卵清蛋白(OVA)的γ-PGANP进行皮下免疫比使用弗氏完全佐剂乳化的OVA免疫更有效地抑制了OVA转染的肿瘤的生长。另外,皮下注射后,γ-PGANPs不会引起组织病理学改变,也不会通过静脉注射引起急性毒性。重要的是,γ-PGANP有效地将捕获的抗原蛋白递送到APC中,并且这些捕获抗原的APC迁移到区域淋巴结。我们的结果表明,用于抗原递送的γ-PGANP系统将提高抗癌疫苗的临床实用性。

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