Enzyme-powered Janus platelet cell robots for active and targeted drug delivery

被引:330
作者
Tang, Songsong [1 ,2 ,3 ]
Zhang, Fangyu [1 ,2 ]
Gong, Hua [1 ,2 ]
Wei, Fanan [1 ,2 ]
Zhuang, Jia [1 ,2 ]
Karshalev, Emil [1 ,2 ]
de Avila, Berta Esteban-Fernandez [1 ,2 ]
Huang, Chuying [1 ,2 ]
Zhou, Zhidong [1 ,2 ]
Li, Zhengxing [1 ,2 ]
Yin, Lu [1 ,2 ]
Dong, Haifeng [3 ]
Fang, Ronnie H. [1 ,2 ]
Zhang, Xueji [3 ]
Zhang, Liangfang [1 ,2 ]
Wang, Joseph [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept NanoEngn, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Chem Engn Program, La Jolla, CA 92093 USA
[3] Univ Sci & Technol Beijing, Res Ctr Bioengn & Sensing Technol, Beijing 100083, Peoples R China
基金
中国国家自然科学基金;
关键词
DOXORUBICIN; DRIVEN;
D O I
10.1126/scirobotics.aba6137
中图分类号
TP24 [机器人技术];
学科分类号
080202 ; 1405 ;
摘要
Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.
引用
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页数:11
相关论文
共 63 条
[1]   Surface Engineering for Cell-Based Therapies: Techniques for Manipulating Mammalian Cell Surfaces [J].
Abbina, Srinivas ;
Siren, Erika M. J. ;
Moon, Haisle ;
Kizhakkedathu, Jayachandran N. .
ACS BIOMATERIALS SCIENCE & ENGINEERING, 2018, 4 (11) :3658-3677
[2]   Soft erythrocyte-based bacterial microswimmers for cargo delivery [J].
Alapan, Yunus ;
Yasa, Oncay ;
Schauer, Oliver ;
Giltinan, Joshua ;
Tabak, Ahmet F. ;
Sourjik, Victor ;
Sitti, Metin .
SCIENCE ROBOTICS, 2018, 3 (17)
[3]   Intrinsic enzymatic properties modulate the self-propulsion of micromotors [J].
Arque, Xavier ;
Romero-Rivera, Adrian ;
Feixas, Ferran ;
Patino, Tania ;
Osuna, Silvia ;
Sanchez, Samuel .
NATURE COMMUNICATIONS, 2019, 10 (1)
[4]   The ins and outs of endocytic trafficking in platelet functions [J].
Banerjee, Meenakshi ;
Whiteheart, Sidney W. .
CURRENT OPINION IN HEMATOLOGY, 2017, 24 (05) :467-474
[5]   PH-INDUCED DENATURATION OF SPECTRIN CHANGES THE INTERACTION OF MEMBRANE-PROTEINS IN ERYTHROCYTE-GHOSTS - BIOCHEMICAL AND ELECTRON-MICROSCOPIC EVIDENCE [J].
BAUMANN, E ;
LINSS, W ;
FROHNER, M ;
STOYA, G ;
RICHTER, W .
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 1994, 176 (01) :93-99
[6]   Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials [J].
Blokhina, Svetlana V. ;
Sharapova, Angelica V. ;
O'khovich, Marina V. ;
Volkova, Tatyana V. ;
Perlovich, German L. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 93 :29-37
[7]   Circulatory-cell-mediated nanotherapeutic approaches in disease targeting [J].
Burnouf, Thierry ;
Burnouf, Pierre-Alain ;
Wu, Yu-Wen ;
Chuang, Er-Yuan ;
Lu, Long-Sheng ;
Goubran, Hadi .
DRUG DISCOVERY TODAY, 2018, 23 (05) :934-943
[8]   Small-Scale Machines Driven by External Power Sources [J].
Chen, Xiang-Zhong ;
Jang, Bumjin ;
Ahmed, Daniel ;
Hu, Chengzhi ;
De Marco, Carmela ;
Hoop, Marcus ;
Mushtaq, Fajer ;
Nelson, Bradley J. ;
Pane, Salvador .
ADVANCED MATERIALS, 2018, 30 (15)
[9]   Targeting platelet function to improve drug delivery [J].
Demers, Melanie ;
Wagner, Denisa D. .
ONCOIMMUNOLOGY, 2012, 1 (01) :100-102
[10]   Square-wave voltammetric determination of hydroxychloroquine in pharmaceutical and synthetic urine samples using a cathodically pretreated boron-doped diamond electrode [J].
Deroco, Patricia Batista ;
Vicentini, Fernando Campanha ;
Oliveira, Geiser Gabriel ;
Rocha-Filho, Romeu C. ;
Fatibello-Filho, Orlando .
JOURNAL OF ELECTROANALYTICAL CHEMISTRY, 2014, 719 :19-23