Synthetic Cells Synthesize Therapeutic Proteins inside Tumors

Adv Healthc Mater. 2018 May;7(9):e1701163. doi: 10.1002/adhm.201701163. Epub 2017 Dec 28.


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 × 107 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.

Keywords: biologics; breast cancer; nanoparticles; nanotechnology; origin of life; personalized medicine; protein drugs; protocells; synthetic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / biosynthesis*
  • Animals
  • Artificial Cells / metabolism*
  • Bacterial Toxins / biosynthesis*
  • Cell Line, Tumor
  • Exotoxins / biosynthesis*
  • Female
  • Green Fluorescent Proteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy
  • Pseudomonas aeruginosa Exotoxin A
  • Tumor Microenvironment*
  • Virulence Factors / biosynthesis*


  • Bacterial Toxins
  • Exotoxins
  • Virulence Factors
  • Green Fluorescent Proteins
  • ADP Ribose Transferases