中国科学院福建物质结构研究所陈学元团队开发了基于稀土核苷酸自组装的肿瘤微环境响应性生物降解纳米制剂用于精确癌症治疗。相关研究成果于2022年1月27日发表在国际知名学术期刊《德国应用化学》。

刺激响应性纳米制剂能同时满足正常组织清除和肿瘤特异性反应性治疗，对精确的癌症治疗极具吸引力。

该文中，研究人员开发了一种独特的模板诱导自组装策略，用于精细控制合成具有非晶态结构和可调尺寸（从亚5 nm到105 nm）的自组装镧系元素（Ln³⁺）核苷酸纳米颗粒（LNNPs）。借助低温（10 K）和高分辨率光谱，首次揭示了LNNPs中Ln³⁺的局部位置对称性。进一步证明所提出的LNNPs具有高效负载阿霉素和肿瘤微环境响应性释放阿霉素的能力。尤其是，低于5纳米LNNPs不仅具有良好的生物相容性和优越的肾脏清除性能，而且能够有效地保留肿瘤。

研究发现揭示了LNNPs作为新一代治疗平台的巨大潜力，以克服纳米药物的有效治疗和长期毒性之间的困境，用于未来的临床应用。

附：英文原文

Title: Tumor-Microenvironment-Responsive Biodegradable Nanoagents Based on Lanthanide Nucleotide Self-Assemblies toward Precise Cancer Therapy

Author: Yingjie Yang, Yan Liu, Datao Tu, Mingmao Chen, Yunqin Zhang, Hang Gao, Xueyuan Chen

Issue&Volume: 2022-01-27

Abstract: Stimuli-responsive nanoagents, which simultaneously satisfy normal tissue clearance and tumor-specific responsive treatment, are highly attractive for precise cancer theranostics. Herein, we develop a unique template-induced self-assembly strategy for the exquisitely controlled synthesis of self-assembled lanthanide (Ln3+) nucleotide nanoparticles (LNNPs) with amorphous structure and tunable size from sub-5 nm to 105 nm. By virtue of the low-temperature (10 K) and high-resolution spectroscopy, the local site symmetry of Ln3+ in LNNPs is unraveled for the first time. The proposed LNNPs are further demonstrated to possess the ability for highly efficient loading and tumor-microenvironment-responsive release of doxorubicin. Particularly, sub-5 nm LNNPs not only exhibit excellent biocompatibility and predominant renal-clearance performance, but also enable efficient tumor retention. These findings reveal the great potential of LNNPs as a new generation of therapeutic platform to overcome the dilemma between efficient therapy and long-term toxicity of nanoagents for future clinical applications.

DOI: 10.1002/anie.202116983

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202116983