蛋白冠與納米藥物調(diào)控策略

陳春英*

國家納米科學(xué)中心，北京，100190

*Email: chenchy@nanoctr.cn

 

納米顆粒/納米藥物一旦進(jìn)入生命體系，將面對(duì)復(fù)雜的多重生物屏障和生理結(jié)構(gòu)，納米材料/納米藥物與不同組織器官、細(xì)胞、生物流體微環(huán)境等復(fù)雜納米-生物界面的互作方式是決定其被遞送到目標(biāo)部位的核心步驟。其中，生物流體的生物分子迅速與納米顆粒表面結(jié)合，如納米與血液蛋白分子互作形成的“納米蛋白冠”作為起始步驟，對(duì)納米顆粒體內(nèi)的輸運(yùn)和命運(yùn)影響巨大，引起了科學(xué)界的廣泛關(guān)注。蛋白冠的存在不僅會(huì)影響和調(diào)控納米顆粒在生物體內(nèi)的行為、代謝過程及其最終的命運(yùn)，進(jìn)而也會(huì)影響納米藥物生物醫(yī)學(xué)功能的發(fā)揮；與納米藥物遞送技術(shù)的多個(gè)瓶頸問題，如長循環(huán)、肝脾富集、免疫原性等現(xiàn)象密切相關(guān)。

如何揭示“納米蛋白冠”對(duì)納米顆粒體內(nèi)命運(yùn)的影響是長期面臨的巨大挑戰(zhàn)。其中，缺乏跨尺度、高靈敏、原位表征的技術(shù)手段是制約其發(fā)展的關(guān)鍵瓶頸問題。我們提出了納米蛋白冠的原位表征、多種同步輻射分析技術(shù)和代謝分析方法聯(lián)合應(yīng)用的研究策略，通過發(fā)展多種同步輻射分析技術(shù)，實(shí)現(xiàn)高靈敏、高分辨地原位解析納米材料在靶組織、靶細(xì)胞內(nèi)的分布及其化學(xué)形態(tài)；闡明體內(nèi)納米材料的生物化學(xué)轉(zhuǎn)化過程。蛋白冠的形成受到納米材料及其理化特性的影響，包括尺寸、結(jié)構(gòu)、晶型和表面修飾分子的種類、電荷、手性等。同時(shí)，這些性質(zhì)將影響生物分子與納米材料相互作用的位點(diǎn)、分子取向以及生物活性等。本報(bào)告將重點(diǎn)闡述納米蛋白冠的化學(xué)生物學(xué)性質(zhì)以及如何指導(dǎo)納米藥物的理性設(shè)計(jì)與臨床轉(zhuǎn)化。

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

關(guān)鍵詞：納米蛋白冠；納米藥物；體內(nèi)命運(yùn)；理性設(shè)計(jì)

參考文獻(xiàn)

[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.

 

 

陳春英，中國科學(xué)院院士，國家納米科學(xué)中心研究員，新基石研究員。先后擔(dān)任國家重點(diǎn)研發(fā)計(jì)劃“納米科技”、“納米前沿”重點(diǎn)專項(xiàng)首席科學(xué)家。

長期在分析化學(xué)領(lǐng)域，從事納米蛋白冠分析與納米藥物分析，建立納米顆粒生物體內(nèi)行為的檢測方法與機(jī)制，發(fā)現(xiàn)了納米顆粒體內(nèi)命運(yùn)的隱身效應(yīng)、遠(yuǎn)端效應(yīng)、生物可利用效應(yīng)等關(guān)鍵化學(xué)生物學(xué)特性，成為藥物遞送領(lǐng)域的重要分析方法和依據(jù)，被制定為多項(xiàng)ISO和國家標(biāo)準(zhǔn)。在Nature Nanotechnology, Nature Methods, Nature Protocols, Science Advances, National Science Review, CCS Chemistry, PNAS, JACS, Angew Chem等期刊發(fā)表論文400余篇，取得了系統(tǒng)性的研究成果，先后兩次獲得國家自然科學(xué)獎(jiǎng)二等獎(jiǎng)，榮獲全國五一巾幗標(biāo)兵、IUPAC化學(xué)化工杰出女性獎(jiǎng)、TWAS 化學(xué)獎(jiǎng)、RSC Environment Prize、中國青年女科學(xué)家獎(jiǎng)等。目前擔(dān)任ACS Nano執(zhí)行主編以及National Science Review， Science Bulletin等多個(gè)期刊的編委。目前擔(dān)任中國化學(xué)會(huì)理事、女化學(xué)工作者委員會(huì)副主任委員等。2023年當(dāng)選為中國化學(xué)會(huì)會(huì)士。