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油包固肽纳米载体用于经皮传递黑素瘤癌症疫苗

Solid-in-Oil Peptide Nanocarriers for Transcutaneous Cancer Vaccine Delivery against Melanoma.

出版信息

Mol Pharm. 2018 Mar 5;15(3):955-961. doi: 10.1021/acs.molpharmaceut.7b00894. Epub 2018 Feb 15.

DOI:10.1021/acs.molpharmaceut.7b00894
PMID:29397746
Abstract

Cancer vaccines represent a prophylactic or therapeutic method of suppressing cancer by activating the adaptive immune system. The immune response is initiated by the delivery of tumor antigens to antigen presenting cells (APCs). The use of peptides as vaccine antigens is advantageous, especially in the availability and productivity of pure and defined antigens. However, their limited immunogenicity remains a major drawback, and therefore, the utilization of nanocarriers as a means of delivering antigens to target cells and/or the addition of immune stimulants have been investigated as an efficient peptide-based cancer vaccine. We have developed a solid-in-oil (S/O) nanodispersion as a transcutaneous nanocarrier for hydrophilic molecules. This system has attractive features as a peptide nanocarrier for cancer vaccines, including transcutaneous targeting of professional APCs in the skin, high encapsulation efficacy of hydrophilic molecules, and capacity for coloading with a variety of immune stimulants such as adjuvants. We therefore sought to utilize the developed S/O nanodispersion for the delivery of the tyrosine-related protein 2 peptide, TRP-2, as a peptide antigen against melanoma. Transcutaneous vaccination of the S/O nanodispersion coloaded with adjuvant R-848 was associated with a significant inhibition of melanoma growth and suppression of lung metastasis in tumor-bearing mice. Our findings indicate the potential of S/O nanodispersions as an endogenous peptide carrier for cancer vaccines.

摘要

癌症疫苗通过激活适应性免疫系统来抑制癌症,代表了一种预防性或治疗性的方法。免疫反应是通过将肿瘤抗原递送至抗原呈递细胞 (APC) 而引发的。使用肽作为疫苗抗原具有优势,特别是在纯净和定义抗原的可用性和产量方面。然而,其有限的免疫原性仍然是一个主要的缺点,因此,已经研究了使用纳米载体作为将抗原递送至靶细胞的手段和/或添加免疫刺激剂作为有效的基于肽的癌症疫苗。我们已经开发了一种固-油 (S/O) 纳米分散体作为亲水性分子的经皮纳米载体。该系统作为癌症疫苗的肽纳米载体具有吸引人的特点,包括皮肤中专业 APC 的经皮靶向、亲水性分子的高包封效率以及与各种免疫刺激剂(如佐剂)共载的能力。因此,我们试图利用开发的 S/O 纳米分散体来递送酪氨酸相关蛋白 2 肽 (TRP-2),作为针对黑色素瘤的肽抗原。与共载佐剂 R-848 的 S/O 纳米分散体经皮接种与黑色素瘤生长的显著抑制和肺转移的抑制有关。我们的研究结果表明,S/O 纳米分散体作为癌症疫苗的内源性肽载体具有潜力。

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