nanoparticles

How many nanoparticle-based drugs reach tumours? Less than one per cent, U of T study shows

lavende4 — Mon, 25 Apr 2016 19:12:32 +0000

How many nanoparticle-based drugs reach tumours? Less than one per cent, U of T study shows lavende4 Mon, 04/25/2016 - 15:12

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Stefan Wilhelm is the lead author of a new review paper that shows less than one per cent of designer nanoparticles actually reach their intended target (photo by Neil Ta)

Tyler Irving

Author legacy

Tyler Irving

Topic

Breaking Research

Cancer

Faculty of Applied Science & Engineering

nanoparticles

Research & Innovation

Faculty & Staff

Subheadline

“Reality check” meta-analysis reveals that only 0.7 per cent of designer nanoparticles reach their intended target

Targeting cancer cells for destruction while leaving healthy cells alone — that has been the promise of the emerging field of cancer nanomedicine. But a new meta-analysis from U of T’s Institute of Biomaterials & Biomedical Engineering (IBBME) indicates that progress so far has been limited and new strategies are needed if the promise is to become reality.

“The amount of research into using engineered nanoparticles to deliver cancer drugs directly to tumours has been growing steadily over the last decade, but there are very few formulations used in patients. The question is why?” says Professor Warren Chan (IBBME, ChemE, MSE), senior author on the review paper published April 26 in Nature Reviews Materials. “We felt it was time to look at the field more closely.”

Chan and his co-authors analysed 117 published papers that recorded the delivery efficiency of various nanoparticles to tumours — that is, the percentage of injected nanoparticles that actually reach their intended target. To their surprise, they found that the median value was about 0.7 per cent of injected nanoparticles reaching their targets, and that this number has not changed for the last ten years. “If the nanoparticles do not get delivered to the tumour, they cannot work as designed for many nanomedicines,” says Chan.

Even more surprising was that altering nanoparticles themselves made little difference in the net delivery efficiency. “Researchers have tried different materials and nanoparticle sizes, different surface coatings, different shapes, but all these variations lead to no difference, or only small differences,” says Stefan Wilhelm, a post-doctoral researcher in Chan’s lab and lead author of the paper. “These results suggest that we have to think more about the biology and the mechanisms that are involved in the delivery process rather than just changing characteristics of nanoparticles themselves.”

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Wilhelm points out that nanoparticles do have some advantages. Unlike chemotherapy drugs which go everywhere in the body, drugs delivered by nanoparticles accumulate more in some organs and less in others. This can be beneficial: for example, one current treatment uses nanoparticles called liposomes to encapsulate the cancer drug doxorubicin.

This encapsulation reduces the accumulation of doxorubicin in the heart, thereby reducing cardiotoxicity compared with administering the drug on its own.

Unfortunately, the majority of injected nanoparticles, including liposomes, end up in the liver, spleen and kidneys, which is logical since the job of these organs is to clear foreign substances and poisons from the blood. This suggests that in order to prevent nanoparticles from being filtered out of the blood before they reach the target tumour, researchers may have to control the interactions of those organs with nanoparticles.

It may be that there is an optimal particle surface chemistry, size, or shape required to access each type of organ or tissue. One strategy the authors are pursuing involves engineering nanoparticles that can dynamically respond to conditions in the body by altering their surfaces or other properties, much like proteins do in nature. This may help them to avoid being filtered out by organs such as the liver, but at the same time to have the optimal properties needed to enter tumors.

More generally, the authors argue that, in order to increase nanoparticle delivery efficiency, a systematic and coordinated long-term strategy is necessary. To build a strong foundation for the field of cancer nanomedicine, researchers will need to understand a lot more about the interactions between nanoparticles and the body’s various organs than they do today. To this end, Chan’s lab has developed techniques to visualize these interactions across whole organs using 3D optical microscopy, a study published in ACS Nano this week.

In addition to this, the team has set up an open online database, called the Cancer Nanomedicine Repository that will enable the collection and analysis of data on nanoparticle delivery efficiency from any study, no matter where it is published. The team has already uploaded the data gathered for the latest paper, but when the database goes live in June, researchers from all over the world will be able to add their data and conduct real-time analysis for their particular area of interest.

“It is a big challenge to collect and find ways to summarize data from a decade of research but this article will be immensely useful to researchers in the field,” says Professor Julie Audet (IBBME), a collaborator on the study.

Wilhelm says there is a long way to go in order to improve the clinical translation of cancer nanomedicines, but he’s optimistic about the results. “From the first publication on liposomes in 1965 to when they were first approved for use in treating cancer, it took 30 years,” he says. “In 2016, we already have a lot of data, so there’s a chance that the translation of new cancer nanomedicines for clinical use could go much faster this time. Our meta-analysis provides a ‘reality’ check of the current state of cancer nanomedicine and identifies the specific areas of research that need to be investigated to ensure that there will be a rapid clinical translation of nanomedicine developments.”

Engineering nanoparticles that can change their shape to deliver cancer drugs to tumours

sgupta — Thu, 18 Feb 2016 14:26:52 +0000

Engineering nanoparticles that can change their shape to deliver cancer drugs to tumours sgupta Thu, 02/18/2016 - 09:26

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“We’re making shape-changing nanoparticles,” Professor Warren Chan says. “They’re a series of building blocks, kind of like a LEGO set.” (photo by NSERC)

Marit Mitchell

Author legacy

Marit Mitchell

Researchers convert microbubbles into nanoparticles to fight cancer

sgupta — Tue, 31 Mar 2015 11:15:45 +0000

Researchers convert microbubbles into nanoparticles to fight cancer sgupta Tue, 03/31/2015 - 07:15

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Professor Gang Zheng

Subheadline

New discovery hold promises for more precise tumour treatment

Researchers at the ��Ƶ have successfully converted microbubbles into nanoparticles that stay trapped in tumours to potentially deliver targeted, therapeutic payloads.

The discovery, published online March 30, 2015 in Nature Nanotechnology, details how Professor Gang Zheng and his research team created a new type of microbubble using a compound called porphyrin – a naturally occurring pigment in nature that harvests light.

In the lab in pre-clinical experiments, the team used low-frequency ultrasound to burst the porphyrin containing bubbles and observed that they fragmented into nanoparticles. Most importantly, the nanoparticles stayed within the tumour and could be tracked using imaging.

“Our work provides the first evidence that the microbubble reforms into nanoparticles after bursting and that it also retains its intrinsic imaging properties,” says Zheng, a professor of medical biophysics at U of T. “We have identified a new mechanism for the delivery of nanoparticles to tumours, potentially overcoming one of the biggest translational challenges of cancer nanotechnology. In addition, we have demonstrated that imaging can be used to validate and track the delivery mechanism."

Conventional microbubbles lose all intrinsic imaging and therapeutic properties once they burst, he says, in a blink-of-an-eye process that takes only a minute or so after bubbles are infused into the bloodstream.

“For clinicians, harnessing microbubble-to-nanoparticle conversion may be a powerful new tool that enhances drug delivery to tumours, prolongs tumour visualization and enables them to treat cancerous tumours with greater precision,” says Zheng, a senior scientist at the Princess Margaret Cancer Centre.

For the past decade, Zheng’s research focus has been on finding novel ways to use heat, light and sound to advance multi-modality imaging and create unique, organic nanoparticle delivery platforms capable of transporting cancer therapeutics directly to tumours.

The research was funded by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship, the Emerging Team Grant on Regenerative Medicine and Nanomedicine co-funded by the CIHR and the Canadian Space Agency, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the International Collaborative R&D Project of the Ministry of Knowledge Economy, South Korea, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation.

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nanoparticles

How many nanoparticle-based drugs reach tumours? Less than one per cent, U of T study shows

Engineering nanoparticles that can change their shape to deliver cancer drugs to tumours

Read more about research from Professor Chan

Researchers convert microbubbles into nanoparticles to fight cancer