Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Cancer Res. 2012 Nov 15;72(22):5956-65. doi: 10.1158/0008-5472.CAN-12-2127.
Brachytherapy is a common clinical technique involving implantation of sealed radioactive "seeds" within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.
近距离治疗是一种常见的临床技术,涉及将密封的放射性“种子”植入肿瘤内,以选择性地辐照肿瘤组织,同时最大限度地减少全身毒性。为了减轻与复杂的手术植入和随后的设备移除程序相关的缺点,我们开发了一种替代方法,使用由热响应弹性蛋白样多肽(ELP)组成的基因编码肽聚合物溶液,该溶液用(131)I 放射性标记,在肿瘤内注射后自组装成放射性核素种子。这些无毒和可生物降解的聚合物种子的形成导致放射性核素在肿瘤内的滞留时间延长(注射后 7 天内约为 85% ID/肿瘤),在两个人类异种移植(FaDu 和 PC-3)中引发了 100%的肿瘤生长延迟,并在单次施用标记的 ELP 后治愈了超过 67%的荷瘤动物。这些结果表明,可生物降解和可注射的含放射性核素多肽种子的原位自组装可能是传统近距离治疗的一种有前途的治疗替代方法。