Hatefi A, Cappello J, Ghandehari H
Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201-1075, USA.
Pharm Res. 2007 Apr;24(4):773-9. doi: 10.1007/s11095-006-9200-5. Epub 2007 Feb 17.
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.
本研究旨在探讨丝素 - 弹性蛋白样蛋白聚合物（SELPs）在体外和体内控制腺病毒释放速率同时保持其生物活性的潜力。
制备了由SELP/腺病毒混合物组成的水凝胶系统。通过实时定量聚合酶链反应（Real Time-PCR）对水凝胶中腺病毒颗粒的释放进行定量，并使用共聚焦显微镜和β - 半乳糖苷酶测定法评估释放病毒的生物活性。为了证明SELP在体内捕获病毒载体并在较长时间内释放它的能力，制备了SELP/腺病毒混合物并直接注射到小鼠的乳腺癌和头颈癌异种移植肿瘤模型中。在不同时间点处死小鼠，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周内释放病毒，同时保持其生物活性。瘤内注射后，观察到腺病毒的长期局部表达。
这些结果表明SELP在将腺病毒局部递送至实体瘤方面具有潜力，可作为瘤内病毒注入的替代方法。
