蛋白冠与纳米药物调控策略

陈春英*

国家纳米科学中心，北京，100190

*Email: chenchy@nanoctr.cn

 

纳米颗粒/纳米药物一旦进入生命体系，将面对复杂的多重生物屏障和生理结构，纳米材料/纳米药物与不同组织器官、细胞、生物流体微环境等复杂纳米-生物界面的互作方式是决定其被递送到目标部位的核心步骤。其中，生物流体的生物分子迅速与纳米颗粒表面结合，如纳米与血液蛋白分子互作形成的“纳米蛋白冠”作为起始步骤，对纳米颗粒体内的输运和命运影响巨大，引起了科学界的广泛关注。蛋白冠的存在不仅会影响和调控纳米颗粒在生物体内的行为、代谢过程及其最终的命运，进而也会影响纳米药物生物医学功能的发挥；与纳米药物递送技术的多个瓶颈问题，如长循环、肝脾富集、免疫原性等现象密切相关。

如何揭示“纳米蛋白冠”对纳米颗粒体内命运的影响是长期面临的巨大挑战。其中，缺乏跨尺度、高灵敏、原位表征的技术手段是制约其发展的关键瓶颈问题。我们提出了纳米蛋白冠的原位表征、多种同步辐射分析技术和代谢分析方法联合应用的研究策略，通过发展多种同步辐射分析技术，实现高灵敏、高分辨地原位解析纳米材料在靶组织、靶细胞内的分布及其化学形态；阐明体内纳米材料的生物化学转化过程。蛋白冠的形成受到纳米材料及其理化特性的影响，包括尺寸、结构、晶型和表面修饰分子的种类、电荷、手性等。同时，这些性质将影响生物分子与纳米材料相互作用的位点、分子取向以及生物活性等。本报告将重点阐述纳米蛋白冠的化学生物学性质以及如何指导纳米药物的理性设计与临床转化。

Fig. 1 Chemical and Biophysical Signatures of the Protein Corona in Nanomedicine

关键词：纳米蛋白冠；纳米药物；体内命运；理性设计

参考文献

[1] Chen, C.Y. et al. Nat. Protoc. 2024, 19: 30.

[2] Chen, C.Y.; Hu, Z.Y.; Zhong, Y.T. et al. Nat. Nanotechnol. 2024, 19: 124.

[3] Zheng, Y.T.; Li, H.C.; Chen, C.Y.; Wang, L.M.; Li, Y. et al. Nat. Nanotechnol. 2022, 17: 993.

[4] Chen, C.Y. et al. Nat. Nanotechnol. 2021, 16: 708.

[5] Chen, C.Y.; Zhu, T. et al. Nat. Nanotechnol. 2019, 14: 719.

[6] Zhou, Y.L.; Wang, L.M.; Chen, C.Y. et al. Nat. Commun. 2022, 13: 5389.

[7] Chen, C.Y.; Qian, P.X. et al. Nat. Commun. 2022, 13: 5657.

[8] Chen, C.Y. et al. JACS, 2022, 144(21): 9184.

 

 

Protein Corona and Strategies for Nanomedicine 

Chunying Chen^*

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China

*Email: chenchy@nanoctr.cn

 

An inconvenient hurdle in the practice of nanomedicine is the protein corona, a spontaneous collection of biomolecular species by nanoparticles in living systems. The protein corona is dynamic in composition and may entail improved water suspendibility and compromised delivery and targeting to the nanoparticles. How much of this nonspecific protein ensemble is determined by the chemistry of the nanoparticle core and its surface functionalization and how much of this entity is dictated by the biological environments that vary spatiotemporally in vivo? How do we “live with” and exploit the protein corona without significantly sacrificing the efficacy of nanomedicines in diagnosing and curing human diseases? Because of the complexity of the biological environment and the dynamic variations in the bioactivity of nanomedicines, in situ, label-free analysis of the transport and transformation of nanomedicines has remained a challenge. Recent improvements in optics, detectors, and light sources have allowed the expansion of advanced light source (ALS) analytical technologies to dig into the underexplored behavior and fate of nanomedicines in vivo.

Thus, in this talk, we will discuss the chemical and biophysical signatures of the protein corona and ponders challenges ahead for the field of nanomedicine. We also discuss the challenges and limitations faced by current approaches and tools and the expectations for the future development of advanced light sources and technologies. Improved ALS imaging and spectroscopy techniques will accelerate a profound understanding of the biological behavior of new nanomedicines.

 

 

陈春英，中国科学院院士，国家纳米科学中心研究员，新基石研究员。先后担任国家重点研发计划“纳米科技”、“纳米前沿”重点专项首席科学家。

长期在分析化学领域，从事纳米蛋白冠分析与纳米药物分析，建立纳米颗粒生物体内行为的检测方法与机制，发现了纳米颗粒体内命运的隐身效应、远端效应、生物可利用效应等关键化学生物学特性，成为药物递送领域的重要分析方法和依据，被制定为多项ISO和国家标准。在Nature Nanotechnology, Nature Methods, Nature Protocols, Science Advances, National Science Review, CCS Chemistry, PNAS, JACS, Angew Chem等期刊发表论文400余篇，取得了系统性的研究成果，先后两次获得国家自然科学奖二等奖，荣获全国五一巾帼标兵、IUPAC化学化工杰出女性奖、TWAS 化学奖、RSC Environment Prize、中国青年女科学家奖等。目前担任ACS Nano执行主编以及National Science Review， Science Bulletin等多个期刊的编委。目前担任中国化学会理事、女化学工作者委员会副主任委员等。2023年当选为中国化学会会士。