Genetically Engineered Algae

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Genetically Engineered Algae

November 15, 2015 by larryhbern

Genetically Engineered Algae

Curator: Larry H. Bernstein, MD, FCAP

Genetically engineered algae kill cancer cells

By Tim Sandle Nov 11, 2015 in Science

http://www.digitaljournal.com/science/are-algae-the-solution-to-beating-cancer/article/449045#ixzz3rZQZ7pRj

A research group in Australia has developed algae nanoparticles. The algae have been found to kill 90 percent of cancer cells in cultured human cells. Based on this success, the modified algae have been shown to destroy cancerous tumors in mice.

Algae is a general term for a range of single-celled microscopic photosynthetic organisms such as diatoms, and larger, multi-cellular plants, like kelp. The use of algae in cancer treatment relates to drug delivery. Some success has been achieved with the use of nanoparticles (such as nanoporous silica) to deliver anti-cancer medicines. One downside with this relates to the cost of production and the fact that some nanoparticles can be toxic. To overcome this, researchers based at the University of South Australia have used algae to model an alternative drug delivery system.

Success has been achieved with microalgae-derived nanoporous biosilica. The bio-material was derived from Thalassiosira pseudonana, which is a species of marine diatom. Diatoms are are among the most common types of phytoplankton, and they are found in the oceans, in freshwater, in soils and on damp surfaces. In studies, modified diatoms have been used as types of backpacks for the targeted delivery of anticancer drugs to tumor sites.

Lead researcher Nico Voelcker, speaking with International Business Times, explained why genetic modification was key in adapting the diatoms: “By genetically engineering diatom algae – tiny, unicellular, photosynthesising algae with a skeleton made of nanoporous silica, we are able to produce an antibody-binding protein on the surface of their shells. Anti-cancer chemotherapeutic drugs are often toxic to normal tissues.”

Although the results are interesting, experiments in cell culture and even on mice do not necessarily translate into success in humans. A series of clinical trials will be required to verify the results and to streamline any potential treatment options.

The research is published in the journal Nature Communications, in a paper headed “Targeted drug delivery using genetically engineered diatom biosilica.”

Targeted drug delivery using genetically engineered diatom biosilica

Bahman Delalat, Vonda C. Sheppard, Soraya Rasi Ghaemi, Shasha Rao, Clive A. Prestidge, Gordon McPhee, Mary-Louise Rogers, et al.

Nature Communications 6,Article number:8791 http://dx.doi.org:/10.1038/ncomms9791

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile ‘backpacks’ for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

Figure 1: The principle of action of the genetically engineered biosilica therapeutic nanoparticles

http://www.nature.com/ncomms/2015/151110/ncomms9791/carousel/ncomms9791-f1.jpg

Genetically engineered diatom biosilica (green) containing liposome-encapsulated drug molecules (yellow) can be targeted to both adherent neuroblastoma cells (red) and lymphocyte cells in suspension (purple) by functionalizing the biosilica

Figure 2: SEM images of T. pseudonana biosilica and analysis of IgG–HRP binding to T. pseudonana biosilica

http://www.nature.com/ncomms/2015/151110/ncomms9791/carousel/ncomms9791-f2.jpg

(a) Side view and (b) top view of cylinder-shaped biosilica from a single diatom cell. (c,d) Details of the biosilica structure showing the highly porous surface. (e) Schematic structure of the S–T8–GFP–GB1 fusion protein. S, N-terminal…

Figure 4: Interaction of anti-CD20 antibody-labelled GB1–biosilica with B and T cells captured on an anti-CD45 antibody microarray.

http://www.nature.com/ncomms/2015/151110/ncomms9791/carousel/ncomms9791-f4.jpg

The left panels show epifluorescence microscopy images of cells captured on microarray spots after incubation with anti-CD20 antibody-labelled biosilica (n=3). The right panels show higher magnification images within the spots. Green: b…

Figure 6: Interaction of anti-p75NTR–GB1–biosilica frustules with adherent cells

http://www.nature.com/ncomms/2015/151110/ncomms9791/carousel/ncomms9791-f6.jpg

(a) Confocal fluorescence microscopy image of SH-SY5Y neuroblastoma cells and (b) BSR fibroblast cells (n=3). Red: actin (phalloidin staining, green: biosilica (GFP-labelled), blue: nucleus (Hoechst 33342 staining). (c) The left panel s…