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Effective and Selective Anti-Cancer Protein Delivery via All-Functions-in-One Nanocarriers Coupled with Visible Light-Responsive, Reversible Protein Engineering

机译：通过多功能合一的纳米载体，结合可见光响应性，可逆蛋白工程技术，有效，选择性地提供抗癌蛋白

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摘要

Efficient intracellular delivery of protein drugs and tumor-specific activation of protein functions are critical toward anti-cancer protein therapy. However, an omnipotent protein delivery system that can harmonize the complicated systemic barriers as well as spatiotemporally manipulate protein function is lacking. Herein, an "all-functions-in-one" nanocarrier doped with photosensitizer (PS) is developed and coupled with reactive oxygen species (ROS)-responsive, reversible protein engineering to realize cancer-targeted protein delivery, and spatiotemporal manipulation of protein activities using long-wavelength visible light (635 nm) at low power density (5 mW cm(-2)). Particularly, RNase A is caged with H2O2-cleavable phenylboronic acid to form 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl carbonate (NBC)-modified RNase (RNBC), which is encapsulated in aciddegradable, ketal-crosslinked PEI (KPEI)-based nanocomplexes (NCs) coated with PS-modified hyaluronic acid (HA). Such NCs harmonize the critical processes for protein delivery, wherein HA coating renders NCs with long blood circulation and cancer cell targeting, and KPEI enables endosomal escape as well as acid-triggered intracellular RNBC release. Tumor-specific light irradiation generates H2O2 to kill cancer cells and restore the protein activity, thus achieving synergistic anti-cancer efficacy. It is the first time to photomanipulate protein functions by coupling ROS-cleavable protein caging with PS-mediated ROS generation, and the "all-functions-in-one" nanocarrier represents a promising example for the programmed anti-cancer protein delivery.
机译：蛋白质药物的有效细胞内递送和蛋白质功能的肿瘤特异性激活对于抗癌蛋白质治疗至关重要。然而，缺乏一种能够协调复杂的系统性障碍以及时空操纵蛋白质功能的全能蛋白质递送系统。本文中，开发了一种掺有光敏剂（PS）的“全功能合一”纳米载体，并将其与活性氧（ROS）响应的可逆蛋白质工程结合，以实现癌症靶向的蛋白质递送和蛋白质活性的时空操纵使用低功率密度（5 mW cm（-2））的长波长可见光（635 nm）。特别地，将RNase A笼罩在H2O2可裂解的苯基硼酸中，以形成4-硝基苯基4-（4,4,5,5-四甲基-1,3,2-二氧杂硼烷-2-基）碳酸苄酯（NBC）修饰的RNase （RNBC），它被包裹在涂有PS修饰的透明质酸（HA）的可酸降解的缩酮交联PEI（KPEI）基纳米复合物（NCs）中。此类NC协调了蛋白质递送的关键过程，其中HA涂层使NC具有长的血液循环和癌细胞靶向作用，而KPEI使内体逃逸以及酸触发的细胞内RNBC释放。肿瘤特异性光照射产生H2O2，杀死癌细胞并恢复蛋白质活性，从而达到协同抗癌功效。这是第一次通过将ROS可裂解的蛋白质笼罩与PS介导的ROS生成偶联来光操纵蛋白质的功能，“全功能合一”的纳米载体代表了有计划的抗癌蛋白质递送的一个有希望的例子。

著录项

  • 来源
    《Advanced Functional Materials》 |2018年第14期|1706710.1-1706710.11|共11页
  • 作者

    He Hua; Chen Yongbing; Li Yongjuan; Song Ziyuan; Zhong Yinan; Zhu Rongying; Cheng Jianjun; Yin Lichen;

  • 作者单位

    Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Joint Int Res Lab Carbon Based Funct Mat & Device, Suzhou 215123, Peoples R China;

    Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Joint Int Res Lab Carbon Based Funct Mat & Device, Suzhou 215123, Peoples R China;

    Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA;

    Soochow Univ, Coll Chem Chem Engn & Mat Sci, Biomed Polymers Lab, Suzhou 215123, Peoples R China;

    Soochow Univ, Affiliated Hosp 2, Dept Cardiothorac Surg, Suzhou 215004, Peoples R China;

    Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA;

    Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Joint Int Res Lab Carbon Based Funct Mat & Device, Suzhou 215123, Peoples R China;

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  • 正文语种 eng
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  • 关键词

    cancer therapy; intracellular protein delivery; light responsiveness; protein caging; ROS responsiveness;

    机译：癌症治疗;细胞内蛋白传递;光反应性;蛋白笼养;ROS反应性;

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