June 11 2017 by Brantley Henson
Whether you are allergic to bees or have ever suffered a particularly nasty sting, we all know a bee sting packs a punch. However, the toxic components of a bee's sting - as well as those of other poisonous stinging insects - may provide medical benefits. The venoms from those painful stings when incorporated into nanoparticle delivery systems may be a key to treating certain diseases and cancers, including HIV.
NANOBEES FIGHT DISEASE
Since 2009, researchers at Washington University in St. Louis and the University of Illinois have been developing ‘nanobees’ for delivering the cytotoxic bee peptide, melittin, to kill cancer cells while protecting healthy cells. Melittin acts as a membranolytic protein that creates holes in cell membranes leading to cell death. In high enough concentration it can destroy any cell it comes into contact with, and would result in destruction of red blood cells (RBCs) if injected into the bloodstream without the nanoparticle packaging.
In the first generation of nanobees, melittin was loaded into the lipid layer of cancer-targeting nanoparticles with a perfluorocarbon core. Perfluorocarbons are good oxygen carriers, and are used often as artificial blood substitutes. Animal studies with the nanobees showed protection of mouse red blood cells and other tissues from melittin, and demonstrated reduced tumor growth for melanoma and breast cancers.1
THE NEW GENERATION OF NANOPARTICLES
Since then, several adaptations have advanced the technology. One recent development is pH activation for cytosolic delivery.2 This helps trigger the nanobees to deliver melittin once endocytosed but before undergoing lysosomal degradation. This technology continues to be applied to cancer and HIV treatments.3 The combination of bee venom and the nanoparticle construct has also shown promise overcoming endosomal entrapment for delivering siRNA to the cytosol with melittin enabling safe and effective endosomolysis.4
OTHER INSECTS WITH USEFUL STINGS
As it turns out, many arthropod venoms carry similar properties as bee venom.5 Researchers have loaded nanoparticles with Mitoparin (found in wasp venom) and TsAP-1 (found in scorpion venom) and also found cancer fighting potential due to their lytic properties.6,7
In the end, these small insects may have larger benefits that simply pollinating our gardens and crops. Through novel applications of nanotechnology it appears that indeed bees and other insects may hold promise in fighting some of today’s most difficult diseases.
- Soman, Neelesh R., et al. "Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth." The Journal of clinical investigation 119.9 (2009): 2830-2842. DOI:10.1172/JCI38842
- Oude Blenke, Erik, et al. "Strategies for the activation and release of the membranolytic peptide melittin from liposomes using endosomal pH as a trigger." Bioconjugate chemistry 28.2 (2017): 574-582. DOI: 10.1021/acs.bioconjchem.6b00677
- Hood, Joshua L., et al. "Cytolytic nanoparticles attenuate HIV-1 infectivity." Antiviral therapy 18.1 (2013): 95-103. DOI: 10.3851/IMP2346
- Hou KK, Pan H, Schlesinger PH, Wickline SA. "A role for peptides in overcoming endosomal entrapment in siRNA delivery - A focus on melittin." Biotechnology advances. 33(6 Pt 1) : 931-40, 2015. DOI: 10.1016/j.biotechadv.2015.05.005.
- Heinen, Tiago Elias, and Ana Beatriz Gorini da Veiga. "Arthropod venoms and cancer." Toxicon 57.4 (2011): 497-511. https://doi.org/10.1016/j.toxicon.2011.01.002
- Misra, Santosh K., et al. "Highly efficient anti-cancer therapy using scorpion ‘NanoVenin’." Chemical Communications 50.87 (2014): 13220-13223. DOI:10.1039/C4CC04748F
- Leite, Natália Bueno, et al. "PE and PS lipids synergistically enhance membrane poration by a peptide with anticancer properties." Biophysical journal 109.5 (2015): 936-947. DOI: 10.1016/j.bpj.2015.07.033