Tag Archives: targeted drug delivery

Therapeutic nanoparticles for agricultural crops

Nanoscale drug delivery systems developed by the biomedical community may prove useful to farmers. The Canadian Broadcasting Corporation (CBC) featured the story in a May 26, 2018 online news item (with audio file; Note: A link has been removed),

Thanks to a fortuitous conversation between an Israeli chemical engineer who works on medical nanotechnology and his farmer friend, there’s a new way to deliver nourishment to nutrient-starved crops.

Avi Schroeder, the chemical engineer and cancer researcher from Technion — Israel Institute of Technology asked his friend what are the major problems facing agriculture today. “He said, ‘You know Avi, one of the major issues we’re facing is that in some of the crops we try to grow, we actually have a lack of nutrients. And then we end up not growing those crops even though they’re very valuable or very important crops.'”

This problem is only going to become more acute in many regions of the world as global population approaches eight billion people.

“Feeding them with healthy food and nutritious food is becoming a major limiting factor. And … the land we can actually grow crops on are also becoming smaller and smaller in every country because people need to build houses too. So what we want is to get actually more crops per hectare.”

The way farmers currently deliver nutrients to malnourished agricultural crops is very inefficient. Much of what is added to the leaves of the plant is wasted. Most of it washes away or isn’t taken up by the plants.

If plants don’t get the nutrients they need, their leaves start to yellow, their growth becomes stunted and they don’t produce as much food as nutrient-rich crops.

“We work primarily in the field of medicine,” says Schroeder. “What we do many times is we’ll load minuscule doses of medicine into nanoparticles — we’ll inject them into the patient. And those nanoparticles will actually be able to detect the disease site inside the body. That sounded very, very similar to the problem the farmers were actually facing — how do you get a medicine into a crop or a nutrient into a crop and get it to the right region within the crop where it’s actually necessary.”

The nanoparticles Schroeder developed are tiny packages that can deliver nutrients — any nutrients — that are placed inside.

A June 6, 2018 news item on Nanowerk offers a few more details,

An innovative technology developed at the Technion [Israel Institute of Technology] could lead to significant increases in agricultural yields. Using a nanometric transport platform on plants that was previously utilized for targeted drug delivery, researchers increased the penetration rate of nutrients into the plants, from 1% to approximately 33%.

A May 27,2018 Technion press release, which originated the news item, fleshes out the details,

The technology exploits nanoscale delivery platforms which until now were used to transport drugs to specific targets in the patient’s body. The work was published in Scientific Reports and will be presented in Nature Press.

The use of the nanotechnology for targeted drug delivery has been the focus of research activity conducted at the Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies at the Wolfson Faculty of Chemical Engineering. The present research repurposes this technology for agricultural use; and is being pursued by laboratory director Prof. Avi Schroeder and graduate student Avishai Karny.

“The constant growth in the world population demands more efficient agricultural technologies, which will produce greater supplies of healthier foods and reduce environmental damage,” said Prof. Schroeder. “The present work provides a new means of delivering essential nutrients without harming the environment.”

The researchers loaded the nutrients into liposomes which are small spheres generated in the laboratory, comprised of a fatty outer layer enveloping the required nutrients. The particles are stable in the plant’s aqueous environment and can penetrate the cells. In addition, the Technion researchers can ‘program’ them to disintegrate and release the load at precisely the location and time of interest, namely, in the roots and leaves. Disintegration occurs in acidic environments or in response to an external signal, such as light waves or heat. The molecules comprising the particles are derived from soy plants and are therefore approved and safe for consumption by both humans and animals.

In the present experiment, the researchers used 100-nanometer liposomes to deliver the nutrients iron and magnesium into both young and adult tomato crops. They demonstrated that the liposomes, which were sprayed in the form of a solution onto the leaves, penetrated the leaves and reached other leaves and roots. Only when reaching the root cells did they disintegrate and release the nutrients. As said, the technology greatly increased the nutrient penetration rate.

In addition to demonstrating the effectivity of this approach as compared to the standard spray method, the researchers also assessed the regulatory limitations associated with the spread of volatile particles.

”Our engineered liposomes are only stable within a short spraying range of up to 2 meters,” explained Prof. Schroeder. “If they travel in the air beyond that distance, they break down into safe materials (phospholipids). We hope that the success of this study will expand the research and development of similar agricultural products, to increase the yield and quality of food crops.”

This is an illustration of the work,

Each liposome (light blue bubble) was loaded with iron and magnesium particles. The liposomes sprayed on the leaves, penetrated and then spread throughout the various parts of the plant and released their load within the cells. Courtesy: Technion

Here’s a link to and a citation for the paper,

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops by Avishai Karny, Assaf Zinger, Ashima Kajal, Janna Shainsky-Roitman, & Avi Schroeder. Scientific Reportsvolume 8, Article number: 7589 (2018) DOI: https://doi.org/10.1038/s41598-018-25197-y Published 17 May 2018

This paper is open access.

Shape-shifting nanoparticles for better chemotherapy from the University of Toronto (Canada)

A research team from the University of Toronto and its shape-shifting nanoparticles are being touted in a Feb. 19, 2016 news item on Nanowerk,

Chemotherapy isn’t supposed to make your hair fall out — it’s supposed to kill cancer cells. A new molecular delivery system created at U of T [University of Toronto] Engineering could help ensure that chemotherapy drugs get to their target while minimizing collateral damage.

Many cancer drugs target fast-growing cells. Injected into a patient, they swirl around in the bloodstream acting on fast-growing cells wherever they find them. That includes tumours, but unfortunately also hair follicles, the lining of your digestive system, and your skin.

U of T Engineering Professor Warren Chan has spent the last decade figuring out how to deliver chemotherapy drugs into tumours — and nowhere else. Now his lab has designed a set of nanoparticles attached to strands of DNA that can change shape to gain access to diseased tissue.

A Feb. 18, 2016 University of Toronto news release (also on EurekAlert), which originated the news item, expands on the theme,

“Your body is basically a series of compartments,” says Chan. “Think of it as a giant house with rooms inside. We’re trying to figure out how to get something that’s outside, into one specific room. One has to develop a map and a system that can move through the house where each path to the final room may have different restrictions such as height and width.”

One thing we know about cancer: no two tumours are identical. Early-stage breast cancer, for example, may react differently to a given treatment than pancreatic cancer, or even breast cancer at a more advanced stage. Which particles can get inside which tumours depends on multiple factors such as the particle’s size, shape and surface chemistry.

Chan and his research group have studied how these factors dictate the delivery of small molecules and nanotechnologies to tumours, and have now designed a targeted molecular delivery system that uses modular nanoparticles whose shape, size and chemistry can be altered by the presence of specific DNA sequences.

“We’re making shape-changing nanoparticles,” says Chan. “They’re a series of building blocks, kind of like a LEGO set.” The component pieces can be built into many shapes, with binding sites exposed or hidden. They are designed to respond to biological molecules by changing shape, like a key fitting into a lock.

These shape-shifters are made of minuscule chunks of metal with strands of DNA attached to them. Chan envisions that the nanoparticles will float around harmlessly in the blood stream, until a DNA strand binds to a sequence of DNA known to be a marker for cancer. When this happens, the particle changes shape, then carries out its function: it can target the cancer cells, expose a drug molecule to the cancerous cell, tag the cancerous cells with a signal molecule, or whatever task Chan’s team has designed the nanoparticle to carry out.

“We were inspired by the ability of proteins to alter their conformation — they somehow figure out how to alleviate all these delivery issues inside the body,” says Chan. “Using this idea, we thought, ‘Can we engineer a nanoparticle to function like a protein, but one that can be programmed outside the body with medical capabilities?’”

Applying nanotechnology and materials science to medicine, and particularly to targeted drug delivery, is still a relatively new concept, but one Chan sees as full of promise. The real problem is how to deliver enough of the nanoparticles directly to the cancer to produce an effective treatment.

“Here’s how we look at these problems: it’s like you’re going to Vancouver from Toronto, but no one tells you how to get there, no one gives you a map, or a plane ticket, or a car — that’s where we are in this field,” he says. “The idea of targeting drugs to tumours is like figuring out how to go to Vancouver. It’s a simple concept, but to get there isn’t simple if not enough information is provided.”

“We’ve only scratched the surface of how nanotechnology ‘delivery’ works in the body, so now we’re continuing to explore different details of why and how tumours and other organs allow or block certain things from getting in,” adds Chan.

He and his group plan to apply the delivery system they’ve designed toward personalized nanomedicine — further tailoring their particles to deliver drugs to your precise type of tumour, and nowhere else.

Here are links to and citations for the team’s two published papers,

DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction by Seiichi Ohta, Dylan Glancy, Warren C. W. Chan. Science  19 Feb 2016: Vol. 351, Issue 6275, pp. 841-845 DOI: 10.1126/science.aad4925

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology by Edward A. Sykes, Qin Dai, Christopher D. Sarsons, Juan Chen, Jonathan V. Rocheleau, David M. Hwang, Gang Zheng, David T. Cramb, Kristina D. Rinker, and Warren C. W. Chan. PNAS     doi: 10.1073/pnas.1521265113 published online Feb. 16, 2016.

Both papers are behind paywalls.