Genetically Encoded Nanoparticles Synthesized Intracellularly

Despite major advances in detection and therapy, multiple cancers are still aggressive and incurable. Metal nanoparticles are being tested and used for tumor imaging, radiotherapy, and hyperthermia. However, using nanoparticles in living specimens is impeded as they often fail to reach the target cell or desired subcellular organelle, causing insufficient efficacy and safety concerns. Sophisticated chemical coatings and targeting aids such as vesicles and antibodies designed to address these pitfalls, provide only a partial solution, as they either increase off-target activity or hinder the clinical function of the nanoparticles. To solve this, we had the nanoparticles of interest made by the tumor cells, using their own genetic machinery. We expressed genes that encode nanoscale protein cages, able to stabilize metal ions inside tumor cells. The expressing tumor cells were presented with subtoxic concentrations of salts containing metal ions, which were stabilized to form metal nanoparticles. We are now testing the hypothesis that creating Genetically Encoded Nanoparticles Synthesized Intracellularly (GENSIs) can yield high-efficiency cancer therapy. We optimized the formation of GENSIs in glioma cell cultures and confirmed the formation of metal GENSIs by optical microscopy, transmission electron microscopy (TEM) and elemental analysis (EDX). We anticipate tumor cell photothermal killing, by expressing GENSIs in cancer cell lines and exposing them to near-infrared laser light. These studies will unlock the immense potential embedded in genetically encoded nanoparticles for cancer therapeutics and diagnostics applications.