辐射防护始终是核工业、核医学和太空探索领域面临的重大挑战。尽管天然氨基酸及其衍生物在体内辐射防护方面展现出潜力，但其原子序数低、代谢迅速等缺陷限制了实际应用。近日，北京师范大学曹玮教授与清华大学许华平教授合作发表了一项创新性研究成果，成功通过仿生聚合策略，将高原子序数的碲元素引入氨基酸聚合物结构中，开发出一种新型碲代胱氨酸仿生黑色素纳米颗粒（TeMNPs），显著提升了辐射防护性能。

  2026年4月7日，相关研究以Biomimetic Polymerization of Tellurocysteine: Breaking the Natural Amino Acid Radioprotection Limitation为题发表在《Advanced Science》上。论文通讯作者为北京师范大学化学学院曹玮教授和清华大学化学系许华平教授，第一作者为清华大学化学系博士后陈伟，第一完成单位为北京师范大学化学学院。

图1. Illustration of the bio-inspired synthesis of TeMNPs and the proposed mechanisms against radiation. Due to the increased average atomic number of melanin, the primary interaction between radiation photons and melanin shifts from Compton scattering to the photoelectric effect. The photoelectric effect cross-section is approximately proportional to Z?^-?, whereas Compton scattering cross-section exhibits only a linear dependence on atomic number. Consequently, the novel melanin synthesized through tellurocysteine polymerization demonstrates exceptional radiation protection performance.

图2. Synthesis and characterization of TeMNPs. (a) Synthetic route for TeMNPs via oxidative copolymerization of tellurocysteine and L-DOPA in water at pH 7 (The chemical structure of TeMNPs was inferred from the detected reaction intermediates). (b) Representative TEM image of the synthetic TeMNPs. (c) Optical images of TeMNPs suspensions. (d) STEM-HAADF image of TeMNPs and the corresponding EDX elemental mappings. (e) ¹³C ssNMR spectra of the synthetic TeMNPs from tellucysteine and L-DOPA. (f) XPS spectra of the synthetic TeMNPs. (g) Mass spectra of intermediate during the synthesis of TeMNPs.

图3. Therapeutic effects on radiation-induced intestinal injury in mice. (a) Schematic illustration of therapeutic experiments with different groups in radiation-induced intestinal injury models. (b) Mice weight was measured after the indicated treatment. (c) Representative H&E staining images of intestinal tissue in each group at 7 days. (d) The proliferation-related Ki-67 was marked to label proliferative active cells. (e) Immunofluorescence images of claudin-1, ZO-1 and occluding in the intestinal tract. (f) Intestinal tissue inflammation levels measured by ELISA kits. (g) Bio-TEM images of mouse intestine with various treatments at 7 days. n = 6 mice per group.

  受微生物中天然黑色素结构的启发，研究团队利用碲代胱氨酸独特的亲核取代反应活性，在温和的水相条件下与左旋多巴发生氧化共聚，成功合成了这种新型碲基纳米材料。碲的原子序数为52，远高于天然黑色素中的碳、氧、氮等轻元素。根据辐射物理原理，当材料原子序数提高后，其与高能光子的相互作用机制将从康普顿散射为主转向光电效应为主——后者的作用截面与原子序数的4至5次方成正比。实验数据显示，TeMNPs的CT值在15 mg/mL浓度下达66.7 Hounsfield单位，显著优于此前报道的硒基黑色素材料。除物理屏蔽效应外，TeMNPs还保留了黑色素固有的自由基清除能力。细胞水平研究证实，TeMNPs能够被肠道上皮细胞和皮肤角质形成细胞高效摄取，并在细胞核周围形成保护性“帽状结构”，有效减轻γ射线诱导的DNA损伤和细胞周期阻滞。通过口服方式给予TeMNPs，发现其在小鼠胃肠道中可维持长达36小时的滞留时间。经全身照射处理后，TeMNPs治疗组小鼠的肠道组织结构完整性显著优于对照组，肠上皮细胞凋亡减少，增殖能力恢复，肠道屏障相关蛋白（如Claudin-1、ZO-1和Occludin）表达水平得到良好维持。转录组分析进一步揭示，TeMNPs能够调节多条与炎症、免疫和细胞死亡相关的信号通路，从而发挥综合防护效果。TeMNPs不仅具备口服给药的便利性，还展现出良好的生物安全性，未来有望用于临床放疗并发症的缓解，甚至为长期太空探索任务提供辐射防护支持。

  这项工作更重要的意义在于，证明了通过将非金属重原子战略性引入生物分子结构中，可以突破天然氨基酸辐射防护能力的固有局限，为新一代的辐射防护制剂的设计提供的全新的思路。

  本研究获得高技术中心重点研发计划、国家自然科学基金、北京师范大学等资助。特此感谢！

  原文链接：https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202600010

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