Mendez Natalie, Herrera Vanessa, Zhang Lingzhi, Hedjran Farah, Feuer Ralph, Blair Sarah L, Trogler William C, Reid Tony R, Kummel Andrew C
Department of Materials Science and Engineering, University of California, San Diego (UCSD), La Jolla, CA, USA.
Department of Bioengineering, UCSD, La Jolla, CA, USA.
Biomaterials. 2014 Nov;35(35):9554-61. doi: 10.1016/j.biomaterials.2014.08.010. Epub 2014 Aug 22.
Oncolytic viruses (OVs) constitute a promising class of cancer therapeutics which exploit validated genetic pathways known to be deregulated in many cancers. To overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, a method for liposomal encapsulation of adenovirus has been developed. The encapsulation of adenovirus in non-toxic anionic lecithin-cholesterol-PEG liposomes ranging from 140 to 180 nm in diameter have been prepared by self-assembly around the viral capsid. The encapsulated viruses retain their ability to infect cancer cells. Furthermore, an immunoprecipitation (IP) technique has shown to be a fast and effective method to extract non-encapsulated viruses and homogenize the liposomes remaining in solution. 78% of adenovirus plaque forming units were encapsulated and retained infectivity after IP processing. Additionally, encapsulated viruses have shown enhanced transfection efficiency up to 4 × higher compared to non-encapsulated Ads. Extracting non-encapsulated viruses from solution may prevent an adverse in vivo immune response and may enhance treatment for multiple administrations.
溶瘤病毒(OVs)是一类很有前景的癌症治疗药物,它们利用了许多癌症中已知失调的经过验证的遗传途径。为了克服免疫反应并增强其治疗原发性和转移性肿瘤的潜在用途,已经开发出一种腺病毒脂质体包封方法。通过围绕病毒衣壳自组装,制备了直径在140至180纳米之间的无毒阴离子卵磷脂 - 胆固醇 - 聚乙二醇脂质体对腺病毒进行包封。包封后的病毒保留了感染癌细胞的能力。此外,免疫沉淀(IP)技术已被证明是一种快速有效的方法,用于提取未包封的病毒并使溶液中残留的脂质体均匀化。78%的腺病毒空斑形成单位在IP处理后被包封并保留了感染性。此外,与未包封的腺病毒相比,包封后的病毒转染效率提高了4倍。从溶液中提取未包封的病毒可以防止体内产生不良免疫反应,并可能增强多次给药的治疗效果。