Nanoparticles disguised as human platelets could greatly enhance the healing power of drug treatments for cardiovascular disease and systemic bacterial infections. These platelet-mimicking nanoparticles, developed by engineers at the University of California, San Diego, are capable of delivering drugs to targeted sites in the body — particularly injured blood vessels, as well as organs infected by harmful bacteria. Engineers demonstrated that by delivering the drugs just to the areas where the drugs were needed, these platelet copycats greatly increased the therapeutic effects of drugs that were administered to diseased rats and mice.
The research, led by nanoengineers at the UC San Diego Jacobs School of Engineering, was published online Sept. 16 in Nature.
“This work addresses a major challenge in the field of nanomedicine: targeted drug delivery with nanoparticles,” said Liangfang Zhang, a nanoengineering professor at UC San Diego and the senior author of the study. “Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs.”
The study is an excellent example of using engineering principles and technology to achieve “precision medicine,” said Shu Chien, a professor of bioengineering and medicine, director of the Institute of Engineering in Medicine at UC San Diego, and a corresponding author on the study. “While this proof of principle study demonstrates specific delivery of therapeutic agents to treat cardiovascular disease and bacterial infections, it also has broad implications for targeted therapy for other diseases such as cancer and neurological disorders,” said Chien.
The ins and outs of the platelet copycats
On the outside, platelet-mimicking nanoparticles are cloaked with human platelet membranes, which enable the nanoparticles to circulate throughout the bloodstream without being attacked by the immune system. The platelet membrane coating has another beneficial feature: it preferentially binds to damaged blood vessels and certain pathogens such as MRSA bacteria, allowing the nanoparticles to deliver and release their drug payloads specifically to these sites in the body.
Enclosed within the platelet membranes are nanoparticle cores made of a biodegradable polymer that can be safely metabolized by the body. The nanoparticles can be packed with many small drug molecules that diffuse out of the polymer core and through the platelet membrane onto their targets.
To make the platelet-membrane-coated nanoparticles, engineers first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the platelet membranes from the platelet cells. Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of nanoparticle cores. The resulting platelet-membrane-coated nanoparticles are approximately 100 nanometers in diameter, which is one thousand times thinner than an average sheet of paper.
This cloaking technology is based on the strategy that Zhang’s research group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing dangerous pore-forming toxins produced by MRSA, poisonous snake bites and bee stings from the bloodstream.
By using the body’s own platelet membranes, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens and proteins naturally present on platelet membranes. This is unlike other efforts, which synthesize platelet mimics that replicate one or two surface proteins of the platelet membrane.
“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” said Zhang. This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, researchers said.
Platelet copycats at work
In one part of this study, researchers packed platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries. Researchers observed that the docetaxel-containing nanoparticles selectively collected onto the damaged sites of arteries and healed them.
When packed with a small dose of antibiotics, platelet-mimicking nanoparticles can also greatly minimize bacterial infections that have entered the bloodstream and spread to various organs in the body. Researchers injected nanoparticles containing just one-sixth the clinical dose of the antibiotic vancomycin into one of group of mice systemically infected with MRSA bacteria. The organs of these mice ended up with bacterial counts up to one thousand times lower than mice treated with the clinical dose of vancomycin alone.
“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” said Zhang. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”
- Che-Ming J. Hu, Ronnie H. Fang, Kuei-Chun Wang, Brian T. Luk, Soracha Thamphiwatana, Diana Dehaini, Phu Nguyen, Pavimol Angsantikul, Cindy H. Wen, Ashley V. Kroll, Cody Carpenter, Manikantan Ramesh, Vivian Qu, Sherrina H. Patel, Jie Zhu, William Shi, Florence M. Hofman, Thomas C. Chen, Weiwei Gao, Kang Zhang, Shu Chien, Liangfang Zhang. Nanoparticle biointerfacing by platelet membrane cloaking. Nature, 2015; DOI: 10.1038/nature15373
Researchers have developed a new design for a cloaking device that overcomes some of the limitations of existing “invisibility cloaks.” In a new study, electrical engineers at the Univ. of California, San Diego have designed a cloaking device that is both thin and does not alter the brightness of light around a hidden object. The technology behind this cloak will have more applications than invisibility, such as concentrating solar energy and increasing signal speed in optical communications. “Invisibility may seem like magic at first, but its underlying concepts are familiar to everyone. All it requires is a clever manipulation of our perception,” said Boubacar Kanté, a professor in the Dept. of Electrical and Computer Engineering at the UC San Diego Jacobs School of Engineering and the senior author of the study. “Full invisibility still seems beyond reach today, but it might become a reality in the near future thanks to recent progress in cloaking devices.” As their name implies, cloaks are devices that cover objects to make them appear invisible. The idea behind cloaking is to change the scattering of electromagnetic waves—such as light and radar—off an object to make it less detectable to these wave frequencies. One of the drawbacks of cloaking devices is that they are typically bulky.
An extremely thin cloaking device is designed using dielectric materials. The cloak is a thin Teflon sheet (light blue) embedded with many small, cylindrical ceramic particles (dark blue). Image: Li-Yi Hsu/UC San Diego
“Previous cloaking studies needed many layers of materials to hide an object, the cloak ended up being much thicker than the size of the object being covered,” said Li-Yi Hsu, electrical engineering PhD student at UC San Diego and the first author of the study, which was recently published in Progress In Electromagnetics Research. “In this study, we show that we can use a thin single-layer sheet for cloaking.” The researchers say that their cloak also overcomes another fundamental drawback of existing cloaking devices: being “lossy.” Cloaks that are lossy reflect light at a lower intensity than what hits their surface. “Imagine if you saw a sharp drop in brightness around the hidden object, it would be an obvious telltale. This is what happens when you use a lossy cloaking device,” said Kanté. “What we have achieved in this study is a ‘lossless’ cloak. It won’t lose any intensity of the light that it reflects.” Many cloaks are lossy because they are made with metal particles, which absorb light. The researchers report that one of the keys to their cloak’s design is the use of non-conductive materials called dielectrics, which unlike metals do not absorb light. This cloak includes two dielectrics, a proprietary ceramic and Teflon, which are structurally tailored on a very fine scale to change the way light waves reflect off of the cloak. In their experiments, the researchers specifically designed a “carpet” cloak, which works by cloaking an object sitting on top of a flat surface. The cloak makes the whole system—object and surface—appear flat by mimicking the reflection of light off the flat surface. Any object reflects light differently from a flat surface, but when the object is covered by the cloak, light from different points is reflected out of sync, effectively cancelling the overall distortion of light caused by the object’s shape. “This cloaking device basically fools the observer into thinking that there’s a flat surface,” said Kanté. The researchers used Computer-Aided Design software with electromagnetic simulation to design and optimize the cloak. The cloak was modeled as a thin matrix of Teflon in which many small cylindrical ceramic particles were embedded, each with a different height depending on its position on the cloak. “By changing the height of each dielectric particle, we were able to control the reflection of light at each point on the cloak,” explained Hsu. “Our computer simulations show how our cloaking device would behave in reality. We were able to demonstrate that a thin cloak designed with cylinder-shaped dielectric particles can help us significantly reduce the object’s shadow.” “Doing whatever we want with light waves is really exciting,” said Kanté. “Using this technology, we can do more than make things invisible. We can change the way light waves are being reflected at will and ultimately focus a large area of sunlight onto a solar power tower, like what a solar concentrator does. We also expect this technology to have applications in optics, interior design and art.” Source: Univ. of California, San Diego
22 Jun 2015
Physicists at UC San Diego have developed a new way to control the transport of electrical currents through high-temperature superconductors — materials discovered nearly 30 years ago that lose all resistance to electricity at commercially attainable low temperatures.
Their development, detailed in two separate scientific publications, paves the way for the development of sophisticated electronic devices capable of allowing scientists or clinicians to non-invasively measure the tiny magnetic fields in the heart or brain, and improve satellite communications.
‘We believe this new approach will have a significant and far-reaching impact in medicine, physics, materials science and satellite communications,’ said Robert Dynes, a professor of physics and former chancellor of UC San Diego. ‘It will enable the development of a new generation of superconducting electronics covering a wide spectrum, ranging from highly sensitive magnetometers for biomagnetic measurements of the human body to large-scale arrays for wideband satellite communications. In basic science, it is hoped it will contribute to the unravelling of the mysteries of unconventional superconductors and could play a major role in new technologies, such as quantum information science.’
The research team headed by Dynes and Cybart, summarized its achievements in this week’s issue of Applied Physics Letters. Another paper outlining the initial discovery was published online April 27 in the journal Nature Nanotechnology.
The developments breathe new life into the promise of electronics constructed from ceramic materials that become superconducting — that is, lose all resistance to electricity — at temperatures that can be easily achieved in the laboratory with liquid nitrogen, which boils at 77 degrees Kelvin or 77 degrees above absolute zero.
Physicists first discovered high-temperature superconductivity in a copper-oxide materials in 1986, setting off an intense effort to develop new kinds of electronics and other devices with this new material.
‘Scientists and engineers worked with fervor to develop these new exciting materials, but soon discovered that they were much more complicated and difficult to work with than imagined,’ said Dynes. ‘These new materials demanded novel device architectures that proved very difficult to realize.’
The UC San Diego physicists found a way to control electrical transport through these materials by building a device within the superconducting material called a ‘Josephson junction,’ analogous in function to the transistor in semiconductor electronics. It’s composed of two superconducting electrodes separated by about one nanometer or a billionth of a meter.
‘Circuits built from Josephson junctions called Superconducting QUantum Interference Devices (SQUIDS), are used for detectors of extremely small magnetic fields, more than 10 billion times smaller than that of Earth,’ said Dynes. ‘One major drawback to these earlier devices is the low temperatures required for their operation, typically just 4 degrees above absolute zero. This requires intricate and costly cooling systems.’
‘Nearly three decades have passed since the discovery of the first high-temperature superconductor and progress in constructing electronic devices using these materials has been very slow because process control at the sub-10-nanometer scale is required to make high quality Josephson junctions out of these materials,’ he explained.
The UC San Diego physicists teamed up with Carl Zeiss Microscopy in Peabody, Mass., which has a facility capable of generating highly focused beams of helium ions, to experiment with an approach they believed might avoid previous problems.
‘Using the Zeiss Orion’s finely focused helium beam, we irradiated and hence disordered a nanoscale region of the superconductor to create what is called a ‘quantum mechanical tunnel barrier’ and were able to write Josephson circuits directly into a thin film of the oxide superconductor,’ said Shane Cybart, a physicist in Dynes’ laboratory who played a key role in the discoveries. ‘Using this direct-write method we eliminated the lithographic processing and offered the promise of a straightforward pathway to quantum mechanical circuits operating at more practical temperatures.’
‘The key to this method is that these oxide superconductors are very sensitive to the point defects in the crystal lattice caused by the ion beam. Increasing irradiation levels has the effect of increasing resistivity and reducing the superconducting transition temperature,’ said Cybart. ‘At very high irradiation levels the superconductor becomes insulating and no longer conducts or superconducts. This allows us to use the small helium beam to write these tunnel junctions directly into the material.’
The Nature Nanotechnology paper describes the development of the basic Josephson junction, while the Applied Physics Letters paper describes the development of the magnetic field sensor built from two junctions.
The UC San Diego physicists, who filed a patent application to license their discovery, are now collaborating with medical researchers to apply their work to the development of devices that can non-invasively measure the tiny magnetic fields generated within the brain, in order to study brain disorders such as autism and epilepsy in children.
‘In the communications field, we are developing wide bandwidth high data throughput satellite communications,’ said Cybart. ‘In basic science, we are using this technology to study ceramic superconducting materials to help determine the physics governing their operation which could lead to improved materials working at even higher temperatures.’
- E. Y. Cho, M. K. Ma, Chuong Huynh, K. Pratt, D. N. Paulson, V. N. Glyantsev, R. C. Dynes and Shane A. Cybart. YBa2Cu3O7− δ superconducting quantum interference devices with metallic to insulating barriers written with a focused helium ion beam. Applied Physics Letters, 2015 DOI: 10.1063/1.4922640
|Source: UC San Diego|