期刊
ADVANCED HEALTHCARE MATERIALS
卷 7, 期 9, 页码 -出版社
WILEY
DOI: 10.1002/adhm.201701163
关键词
biologics; breast cancer; nanoparticles; nanotechnology; origin of life; personalized medicine; protein drugs; protocells; synthetic cells
资金
- Baroness Ariane de Rothschild Women Doctoral Program
- Technion Integrated Cancer Center (TICC)
- Russell Berrie Nanotechnology Institute
- Lorry I. Lokey Interdisciplinary Center for Life Sciences Engineering
- Pre-Clinical Research Authority staff and the Biomedical Core Facility at the Rappaport Faculty of Medicine
- Israel Ministry of Economy for a Kamin grant [52752]
- Israel Ministry of Science Technology and Space - Office of the Chief Scientist [3-11878]
- Israel Science Foundation [1778/13]
- Israel Cancer Association [2015-0116]
- German-Israeli Foundation for Scientific Research and Development for a GIF Young grant [I-2328-1139.10/2012]
- European Union FP-7 IRG Program for a Career Integration Grant [908049]
- Mallat Family Foundation Grant
- Alon Fellowship
- Taub Fellowship
- [ERC-STG-2015-680242]
Synthetic cells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the origins-of-life. Here, it is shown for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules, up to 2 x 10(7) copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on-demand in diseased tissues.
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