Ristori Sandra, Di Cola Emanuela, Lunghi Carlotta, Richichi Barbara, Nativi Cristina
Department of Chemistry and CSGI, University of Florence, 50019 Sesto F.no, Florence, Italy.
Biochim Biophys Acta. 2009 Dec;1788(12):2518-25. doi: 10.1016/j.bbamem.2009.10.005. Epub 2009 Oct 23.
Therapeutic vaccination with tumor antigens is a new approach in cancer treatment, which aims at inducing immune response while avoiding the side effects generally associated to many conventional therapies. To improve the efficacy of vaccines, suitable carriers may be used. Herein the insertion of a thioether analogue of GM3 lactone (SNeuAC-C14) into liposomes is reported. SNeuAC-C14 is a potential vaccine for the targeting of saccharide-based tumor epitopes. Different liposome formulations were designed to act as carriers and to generate recognition by tumor epitopes. The structural study of pure and loaded liposomes was carried out by synchrotron Small Angle X-ray Scattering and was complemented by Dynamic Light Scattering and Zeta potential measurements. This provided detailed information on relevant properties of the investigated host-guest structures and showed that the active unit of SNeuAC-C14, i.e. its spiro tricyclic moiety, was located in the polar head region of the liposome bilayer, which is an important requirement for recognition phenomena. Moreover, it was found that most of the SNeuAC-C14/liposome complexes were positively charged. The obtained results allow these systems to be considered as candidates to promote immunoresponse in tumor cells.
用肿瘤抗原进行治疗性疫苗接种是癌症治疗中的一种新方法，其目的是诱导免疫反应，同时避免许多传统疗法通常伴随的副作用。为了提高疫苗的疗效，可以使用合适的载体。本文报道了将GM3内酯的硫醚类似物（SNeuAC-C14）插入脂质体。SNeuAC-C14是一种靶向基于糖类的肿瘤表位的潜在疫苗。设计了不同的脂质体制剂作为载体，并通过肿瘤表位产生识别作用。通过同步辐射小角X射线散射对纯脂质体和负载脂质体进行了结构研究，并辅以动态光散射和zeta电位测量。这提供了有关所研究的主客体结构相关性质的详细信息，并表明SNeuAC-C14的活性单元，即其螺三环部分，位于脂质体双层的极性头部区域，这是识别现象的一个重要要求。此外，发现大多数SNeuAC-C14/脂质体复合物带正电荷。所获得的结果使这些系统有望被视为促进肿瘤细胞免疫反应的候选物。
