Tag Archives: theragnostics

Microbubbles reform into nanoparticles after bursting

It seems researchers at the Toronto-based (Canada), Princess Margaret Cancer Centre, have developed a new theranostic tool made of microbubbles used for imaging that are then burst into nanoparticles delivering therapeutics. From a March 30, 2015 news item on phys.org,

Biomedical researchers led by Dr. Gang Zheng at Princess Margaret Cancer Centre have successfully converted microbubble technology already used in diagnostic imaging into nanoparticles that stay trapped in tumours to potentially deliver targeted, therapeutic payloads.

The discovery, published online today [March 30, 2015] in Nature Nanotechnology, details how Dr. 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.

A March 30, 2015 University Health Network news release on EurekAlert, which originated the news item, describes the laboratory research on mice,

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. 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,” says Dr. Zheng, Senior Scientist at the Princess Margaret and also Professor of Medical Biophysics at the University of Toronto.

Conventional microbubbles, on the other hand, 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.

“So 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.”

For the past decade, Dr. 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.

Interesting development, although I suspect there are many challenges yet to be met such as ensuring the microbubbles consistently arrive at their intended destination in sufficient mass to be effective both for imaging purposes and, later, as nanoparticles for drug delivery purposes.

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

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging by Elizabeth Huynh, Ben Y. C. Leung, Brandon L. Helfield, Mojdeh Shakiba, Julie-Anne Gandier, Cheng S. Jin, Emma R. Master, Brian C. Wilson, David E. Goertz, & Gang Zheng. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.25 Published online 30 March 2015

This paper is behind a paywall but a free preview is available via ReadCube Access.

This is one of those times where I’m including the funding agencies and the ‘About’ portions of the news release,

The research published today 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.

About Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca .

I was not expecting to see South Korea or Brazil mentioned in the funding. Generally, when multiple countries are funding research, their own research institutions are also involved. As for the Princess Margaret Cancer Centre being one of the top five such centres internationally, I wonder how these rankings are determined.

Aptamers and theranostics (theragnostics)

A popular concept in some circles, theranostics (sometimes called theragnostics) is a conflation of the words ‘therapeutics’ and ‘diagnostics’. A Feb. 17, 2015 news item on Nanowerk features the use of aptamers as theranostic agents,

Aptamers are composed of short RNA or single-stranded DNA sequences that, when folded into their unique 3D conformation, can bind to their targets with high specifi city and affinity. Although functionally similar to protein antibodies, oligonucleotide aptamers offer several advantages over protein antibodies in biomedical and clinical applications.

Through the enhanced permeability and retention effect, nanomedicines can improve the therapeutic index of a treatment and reduce side effects by enhancing accumulation at the disease site. However, this targets tumors passively and, thus, may not be ideal for targeted therapy.

To construct ligand-directed “active targeting” nanobased delivery systems, aptamer-equipped nanomedicines have been tested for in vitro diagnosis, in vivo imaging, targeted cancer therapy, theranostic approaches, sub-cellular molecule detection, food safety, and environmental monitoring.

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

Aptamers and Their Applications in Nanomedicine by Hongguang Sun and Youli Zu. Small DOI: 10.1002/smll.201403073 Article first published online: 11 FEB 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Here’s an illustration of the theranostic concept,

© Wiley

© Wiley

I have a bit more about aptamers in an Oct. 25, 2011 post featuring an interview with professor Maria DeRosa at the University of Ottawa.

Tackling antibiotic resistance with inhalable nanotherapeutics

A June 25, 2014 news item on Nanowerk highlights PneumoNP a new European Union ‘theragnostic’ research project (Note: Links have been removed) ,

A new research project (PneumoNP) is aimed at tackling antibiotic resistance in respiratory tract infections via the use of inhalable nanotherapeutic compounds. Funded under the FP7 programme by the European Commission, the 4-year long PneumoNP project brings together top research institutes, universities, clinicians and enterprises from 6 EU member states. This novel collaboration will contribute to answer the call of the World Health Organization (WHO), who recently released an alarming report on the global threat of antibiotic resistance.

The project will develop an innovative solution to antibiotic resistance by coupling new antibiotics to inhalable carrier molecules, resulting in more efficient targeting of antibiotics to infection-causing bacteria present in the respiratory tract.

An April 30, 2014 WHO news release details the level of antibiotic resistance,

New WHO report provides the most comprehensive picture of antibiotic resistance to date, with data from 114 countries

A new report by WHO–its first to look at antimicrobial resistance, including antibiotic resistance, globally–reveals that this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance–when bacteria change so antibiotics no longer work in people who need them to treat infections–is now a major threat to public health.

The report, “Antimicrobial resistance: global report on surveillance”, notes that resistance is occurring across many different infectious agents but the report focuses on antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhoea. The results are cause for high concern, documenting resistance to antibiotics, especially “last resort” antibiotics, in all regions of the world.

Key findings from the report include:

Resistance to the treatment of last resort for life-threatening infections caused by a common intestinal bacteria, Klebsiella pneumoniae–carbapenem antibiotics–has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients. In some countries, because of resistance, carbapenem antibiotics would not work in more than half of people treated for K. pneumoniae infections.

Resistance to one of the most widely used antibacterial medicines for the treatment of urinary tract infections caused by E. coli–fluoroquinolones–is very widespread. In the 1980s, when these drugs were first introduced, resistance was virtually zero. Today, there are countries in many parts of the world where this treatment is now ineffective in more than half of patients.

Treatment failure to the last resort of treatment for gonorrhoea–third generation cephalosporins–has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom. More than 1 million people are infected with gonorrhoea around the world every day.

Antibiotic resistance causes people to be sick for longer and increases the risk of death. For example, people with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Resistance also increases the cost of health care with lengthier stays in hospital and more intensive care required.

The suggestions offered for tackling antibiotic resistance will be familiar to many (from the news release),

 People can help tackle resistance by:

  •  using antibiotics only when prescribed by a doctor;
  •  completing the full prescription, even if they feel better;
  •  never sharing antibiotics with others or using leftover prescriptions.

A June 25, 2014 PneumoNP press release describes both the European Union’s response to massive, global antibiotic resistance and the specifics of the new programme (PneumoNP),

In this context, the European Commission launched 15 projects under its7 Framework Programme to fight antimicrobial resistance, with PneumoNP being one of these projects. Started in 2014, the aim of this 4-year project is to develop novel therapeutic and diagnostic tools for bacterial respiratory tract infections, focusing on infections caused by Klebsiella pneumoniae. PneumoNP will pioneer the development of a therapeutic treatment based on a combination of nanocarriers coupled to new antibiotics. This novel combination is expected to enhance the efficiency of antibiotic delivery to the patient. The project is expected to generate:

  • a new inhalable drug system made of a new nanotherapeutic system (an antimicrobial peptide or an active pharmaceutical ingredient and a nanocarrier);
  • a new aerosol technology that will allow direct access to the main focus of infection;
  • an innovative efficiency-efficacy test to follow-up the treatment;
  • a new diagnostic test for faster detection and identification of antibiotic resistance in bacteria causing respiratory infections.

European funding allows PneumoNP to combine scientific research capacities with the expert healthcare capabilities of European enterprises. The result is an interdisciplinary collaboration between 11 teams from 6 EU member states – Spain, Italy, France, Germany, The Netherlands, and Denmark. Each partner has a distinct yet collaborative role according to its own expertise involving a total of 8 work packages.

There is a figure in the news release which illustrates the PneumoNP concept,

Figure 2: PneumoNP concept

Figure 2: PneumoNP concept

There is more information about PneumoNP on its website. I wasn’t able to glean much in the way of technical details (are they using silver nanoparticles, what kind of nanocarriers are they considering, etc.) but I imagine those will emerge with time. There is this from the homepage which features the relatively new (to me) word, theragnostic,

Development of a theragnostic system for the treatment of lung Gram-negative bacterial infections

I assume they are conflating two processes, therapeutics and diagnostics for theragnostics.