Cholesterol-wrapped gene carrier
doi:10.1038/nindia.2012.22 Published online 17 February 2012
New research has shown that carbon nanotubes (CNTs) can be dissolved in cholesterol modified with positively charged organic functional groups. The resulting CNT-loaded cationic cholesterol suspensions could be used to deliver genes to cancer cells.
CNTs — versatile nanomaterials — are not readily soluble in most organic solvents and toxic if used without modifications. Making CNTs biocompatible by modifying them with surfactants and virii has proved harmful to cells.
To overcome these drawbacks, the researchers prepared four types of cationic cholesterol compounds from four organic compounds: pyridinium bromide, methyl pyrrolidinium bromide, methyl morpholinium bromide and diazabicyclo octanium bromide. They dissolved cationic cholesterol compounds in water and added CNTs to form CNT-loaded cationic cholesterol suspensions. They studied the efficacy of both the CNT-loaded and cholesterol-only suspensions to bind and deliver strands of calf thymus to cervical cancer cells using an antibody-tagged organic fluorescent molecule.
The study found that the cholesterol compounds, partially wrapping CNTs as well as the exposed regions of CNTs, possessed a significant affinity towards DNA.
The researchers studied the feasibility of using such a CNT–cationic cholesterol suspension as a gene delivery vehicle in fetal bovine serum, which simulates physiological conditions. In fetal bovine serum, all CNT-cationic cholesterol-DNA complexes showed better stability than cationic cholesterol-DNA complexes devoid of CNTs. In studies with cervical cancer cells, the CNT-loaded cholesterol suspensions attached to and permeated cancer cells better than formulations without CNTs.
"Besides the selective delivery of genes, this research will open up new therapeutic opportunities for silencing rogue genes inside a cancer cell," says lead researcher Santanu Bhattacharya.
The authors of this work are from: Department of Organic Chemistry, Indian Institute of Science, and Chemical Biology Unit, JNCASR, Bangalore, India.