Adenoviral gene delivery to solid tumors by recombinant silk-elastinlike protein polymers
Adenoviral gene delivery to solid tumors by recombinant silk-elastinlike protein polymers
复制标题
DOI：
10.1007/s11095-006-9200-5
复制
发表时间：
2007-04-01
影响因子：
3.7
通讯作者：
Ghandehari, H.
中科院分区：
文献类型：
--
作者：
Hatefi, A.;Cappello, J.;Ghandehari, H.
为研究丝素-弹性蛋白样蛋白聚合物（SELP）在体内外控制腺病毒释放速率同时保持其生物活性的潜力，制备了SELP/腺病毒混合物水凝胶系统。通过真实的Time-PCR定量腺病毒颗粒从水凝胶中的释放，并使用共聚焦显微镜和β-半乳糖苷酶测定来评估释放的病毒的生物活性。为了证明SELP在体内捕获病毒货物并在延长的时间段内释放它的能力，制备SELP/腺病毒混合物并直接注射到小鼠的乳腺癌和头颈癌的异种移植肿瘤模型中。在不同的时间点处死小鼠，解剖肿瘤，并在共聚焦显微镜下研究组织切片。体外研究表明，SELP水凝胶在4周的时间内释放病毒，同时保持其生物活性。肿瘤内注射后，腺病毒的长期和本地化的表达被观察到。这些结果表明，SELP在局部腺病毒输送到实体瘤作为一种替代的方法，肿瘤内病毒输注的潜力。
The purpose of this study was to investigate the potential of silk-elastinlike protein polymers (SELPs) in controlling the release rate of adenoviruses in vitro and in vivo while preserving their bioactivity.A hydrogel system composed of SELP/adenovirus mixture was prepared. The release of the adenovirus particles from the hydrogels was quantified by Real Time-PCR and the bioactivity of the released viruses was evaluated using confocal microscopy and beta-galactosidase assay. To demonstrate the ability of SELP in entrapping virus cargo and releasing it over a prolonged period of time in vivo, a SELP/adenovirus mixture was prepared and injected directly into xenograft tumor models of breast and head and neck cancer in mice. At various time points mice were sacrificed, tumors dissected, and tissue sections studied under confocal microscope.In vitro studies demonstrated that SELP hydrogels release viruses over a period of 4 weeks while preserving their bioactivity. After intratumoral injection, a prolonged and localized expression of adenoviruses was observed.These results suggest the potential of SELPs in local adenoviral delivery to solid tumors as an alternative approach to intratumoral virus infusion.