doi:10.1038/nindia.2012.180 Published online 6 December 2012
New research has shown that flower-shaped nanoparticles of zinc oxide could trigger the growth of new blood vessels. Such nanoparticles will be useful in repairing damaged blood vessels and restoring blood flow to damaged tissues1.
They come as good news for treatment of cardiovascular diseases, ischemic heart, limb diseases and wound healing.
The growth of new blood vessels (angiogenesis) involves the migration, growth and differentiation of endothelial cells, which line the inside wall of blood vessels.
"These ZnO nanoflowers successfully induce proliferation, migration and blood vessel formation in various endothelial cells, known to initiate the growth of new blood vessels," lead researcher Chitta Ranjan Patra from CSIR-Indian Institute of Chemical Technology, Hyderabad told Nature India.
This could open a new avenue in nanomedicine making for an alternative therapy in vascular diseases, where growth of new blood vessels plays a significant role, he said.
The telltale sign of vascular diseases is damaged blood vessels. This means tissues of the affected organs such as the heart run out of blood and vital nutrients triggering massive cell death. This is why researchers use growth factor proteins such as vascular endothelial growth factor (VEGF) to boost the growth of new blood vessels.
However, such therapeutic options are expensive. In addition, VEGF-aided blood vessel formation could also end up nourishing harmful tumours. Nanoparticles seem overcome these drawbacks and have become a preferred choice for biomedical applications. Previous studies have shown that europium oxide nanorods, cerium oxide nanoparticles and carbon nanotubes could help grow new blood vessels.
Although ZnO nanoparticles have exhibited efficiency in sensing and imaging biological cells, its role in blood vessel growth had not yet been investigated. Patra and colleagues synthesized ZnO nanoflowers by exposing a mixture of zinc nitrate and ammonium hydroxide to microwave irradiation in a domestic microwave oven. They carried out experiments with human umbilical vein endothelial cells (HUVECs) and fertilized chicken egg yolks to explore blood vessel-growing potentials of these nanoflowers.
Cell proliferation is one of the vital steps in endothelial cells-mediated angiogenesis. To find signs of cell proliferation, the umbilical vein endothelial cells were treated with nanoflowers, which induced 2.7-fold increases in their proliferation compared to similar untreated cells.
Like proliferation, cell cycle is a vital period which helps accelerate blood vessel generation through cell division and DNA replication. The nanoflowers were found to aid such division and replication in HUVECs making new blood vessels.
The researchers also treated fertilised chicken egg yolks with ZnO nanoflowers to find that as the concentration of the nanoflowers was increased, the formation of matured vascular sprouting increased significantly. In a human endothelial cell-based wound healing system, the nanoflowers also induced cell migration, a vital step in new blood vessel formation.
However, there is a potential risk of such blood vessel-growing agents as they could help proliferate lurking cancer cells. "To avert this, we would like to test the nanoflowers on tumour-bearing animal model and patients. Local application of polymer-encapsulated blood vessel-growing ZnO nanoflowers with the help of tissue engineering could solve the problem," Patra claims.
"The study is interesting because the low concentrations of ZnO nanflowers will be non-toxic and could be assimilated slowly with the biological systems," says Panchanan Pramanik of Indian Institute of Technology, Kharagpur who studies the diagnostic prospect of nanomaterials.
"The findings of this research will have great implications in cancer biology and nanodrug-delivery systems," says Jayant Khandare of Piramal Healthcare Limited, Mumbai, who studies the therapeutic and drug delivery aspects of nanomaterials. However, he warns that the efficacy of the ZnO nanoflowers must be tested in cardiovascular tissues since such cellular systems are very different from chicken egg yolks.
The authors of this work are from: CSIR-Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh & AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India; and Mayo Clinic College of Medicine, Mayo Foundation, Rochester, USA.