Stealth DNA-based carbon nanotubes tunnel into cells to deliver targeted drugs
October 31, 2014
A team led by the Lawrence Livermore scientists has created a new way to selectively deliver drugs to a specific area in the body using carbon nanotubes (CNTs).
(KurzweilAI reported on October 17 a similar attempt to sneak drugs into cells using a DNA-based drug-delivery system: nanoscale “cocoons” made of DNA target cancer cells, tricking the cells into absorbing the cocoon, which then unleashes anticancer drugs.)
“Many good and efficient drugs that treat diseases of one organ are quite toxic to another,” said Aleksandr Noy, an LLNL biophysicist who led the study and is the senior author on the paper appearing in the Oct. 30 issue of the journal Nature. “This is why delivery to a particular part of the body and only releasing it there is much better.”
The DNA-based carbon nanotubes, dubbed “porins,” tunnel through cell membranes. They simulate ion channels, which are used by cells to transport vital chemicals: the short CNTs form tiny pores that transport water, protons, small ions, and DNA.
Porins have significant implications for future health care and bioengineering applications, according to the researchers. In addition to delivering drugs to the body, they could serve as a foundation of novel biosensors and DNA sequencing applications, and be used as components of synthetic cells.*
“We found that these nanopores are a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating biosensors,” Noy said. “We are thinking about CNT porins as a first truly versatile synthetic nanopore that can create a range of applications in biology and materials science.”
The team included colleagues at the Molecular Foundry at the Lawrence Berkeley National Laboratory, University of California Merced and Berkeley campuses, and University of Basque Country in Spain.
* The research showed that CNT porins display many characteristic behaviors of natural ion channels: they spontaneously insert into the membranes, switch between metastable conductance states, and display characteristic macromolecule-induced blockades. The team also found that, as in the biological channels, local channel and membrane charges could control the ionic conductance and ion selectivity of the CNT porins.
Abstract of Stochastic transport through carbon nanotubes in lipid bilayers and live cell membranes
There is much interest in developing synthetic analogues of biological membrane channels1 with high efficiency and exquisite selectivity for transporting ions and molecules. Bottom-up2 and top-down3 methods can produce nanopores of a size comparable to that of endogenous protein channels, but replicating their affinity and transport properties remains challenging. In principle, carbon nanotubes (CNTs) should be an ideal membrane channel platform: they exhibit excellent transport properties4, 5, 6, 7, 8 and their narrow hydrophobic inner pores mimic structural motifs typical of biological channels1. Moreover, simulations predict that CNTs with a length comparable to the thickness of a lipid bilayer membrane can self-insert into the membrane9, 10. Functionalized CNTs have indeed been found to penetrate lipid membranes and cell walls11, 12, and short tubes have been forced into membranes to create sensors13, yet membrane transport applications of short CNTs remain underexplored. Here we show that short CNTs spontaneously insert into lipid bilayers and live cell membranes to form channels that exhibit a unitary conductance of 70–100 picosiemens under physiological conditions. Despite their structural simplicity, these ‘CNT porins’ transport water, protons, small ions and DNA, stochastically switch between metastable conductance substates, and display characteristic macromolecule-induced ionic current blockades. We also show that local channel and membrane charges can control the conductance and ion selectivity of the CNT porins, thereby establishing these nanopores as a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating stochastic sensors.