PDF(Pubmed)
Abstract：
Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.
摘要：
不必要的电离辐射（IR）暴露通常会对正常细胞和器官造成急性和慢性氧化损伤。导致严重的生理甚至危及生命的后果。氨磷汀（AMF）是一种经过验证的辐射防护剂，广泛应用于放疗和化疗医学。但是短的半衰期限制了它的生物利用度和临床应用，仍然是一个巨大的挑战。DNA组装的纳米结构，特别是四面体框架核酸（tFNA）是具有卓越生物安全性的有前途的纳米载体，低生物毒性，运输效率高。tFNA还具有相对长期的维持结构稳定性和优异的内吞能力。因此，我们合成了一种基于tFNA的AMF递送系统，用于多器官辐射防护(tFNA@AMF，也称为纳米套装)。通过建立小鼠意外全身照射(TBI)模型和Lewis肺癌放疗模型,我们证明纳米套装可以通过调节抗凋亡和抗氧化应激的分子生物标志物来保护正常细胞免受IR诱导的DNA损伤。在意外全身照射（TBI）小鼠模型中，纳米套装预处理小鼠表现出令人满意的超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量变化，和造血系统的功能恢复，减少IR引起的多器官病理损伤，保护小鼠免受致命辐射。更重要的是,在Lewis肺癌的放疗模型中，纳米套装显示了对正常器官的选择性放射防护，而没有肿瘤控制的干扰。基于一种方便的基于DNA四面体的纳米载体，这项工作提出了一种高效的AMF传递系统，具有延长的半衰期和增强的多器官辐射防护。这种纳米套装是一种有前途的策略，具有巨大的放射性保护临床翻译潜力。
