Tag Archives: photoacoustic imaging

Biosynthetic melanin nanoparticles enabled by genetically engineered bacterium

A January 13, 2023 news item on phys.org announces research into genetically engineering bacteria so they produce melanin nanoparticles, i.e., biosynthetic melanin nanoparticles, Note: Links have been removed,

Photothermal therapy (PTT) has attracted considerable attention for the treatment of tumors because it is minimally invasive and has spatiotemporal selectivity.

Melanin is a kind of multifunctional pigment found widely in mammals, plants and microbes, with great prospects as a PTT agent for cancer treatment. Unfortunately, commercially available melanin is mainly obtained by chemical synthesis or extraction from sepia, which hinders its large-scale production and causes some potential safety hazards.

Recently, a research team led by Prof. Yan Fei from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, together with Prof. Lin Jing from Shenzhen University and Prof. Xu Xiaohong from Guangdong Medical University, heterologously expressed a tyrosinase gene in Escherichia coli to synthesize melanin nanoparticles under mild and environmentally friendly conditions.

Caption: Schematic illustration of biosynthetic melanin nanoparticles for photoacoustic imaging-guided photothermal therapy. Credit: SIAT [Shenzhen Institute of Advanced Technology]

A January 13, 2023 Chinese Academy of Sciences press release (also on EurekAlert but published January 12, 2023), which originated the news item, provides a little more detail about the research,

The biosynthetic melanin nanoparticles exhibited excellent biocompatibility, good stability, and negligible toxicity. “They had strong absorption in the near-infrared region and higher photothermal conversion efficiency (48.9%) than chemically synthesized melanin-like polydopamine nanoparticles under an 808-nm laser irradiation,” said Prof. YAN.

The researchers further evaluated the photoacoustic imaging performance and antitumor efficacy of biosynthetic melanin nanoparticles. The results showed that the biosynthetic melanin nanoparticles had excellent photoacoustic imaging performance and could be used for photoacoustic imaging-guided photothermal therapy in vivo

“Our study provided an alternative approach to synthesize PTT agents with broad application potential in the diagnosis and treatment of cancer,” said Prof. YAN.

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

Biosynthesis of Melanin Nanoparticles for Photoacoustic Imaging Guided Photothermal Therapy by Meijun Fu, Yuping Yang, Zhaomeng Zhang, Yaling He, Yuanyuan Wang, Chenxing Liu, Xiaohong Xu, Jing Lin, Fei Yan. Small DOI: https://doi.org/10.1002/smll.202205343 First published: 29 December 2022

This paper is behind a paywall.

Drink your spinach juice—illuminate your guts

Contrast agents used for magnetic resonance imaging, x-ray imaging, ultrasounds, and other imaging technologies are not always kind to the humans ingesting them. So, scientists at the University at Buffalo (also known as the State University of New York at Buffalo) have developed a veggie juice that does the job according to a July 11, 2016 news item on Nanowerk (Note: A link has been removed),

The pigment that gives spinach and other plants their verdant color may improve doctors’ ability to examine the human gastrointestinal tract.

That’s according to a study, published in the journal Advanced Materials (“Surfactant-Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging”), which describes how chlorophyll-based nanoparticles suspended in liquid are an effective imaging agent for the gut.

The University of Buffalo has provided an illustration of the work,

A new UB-led study suggests that chlorophyll-based nanoparticles are an effective imaging agent for the gut. The medical imaging drink, developed to diagnose and treat gastrointestinal illnesses, is made of concentrated chlorophyll, the pigment that makes spinach green. Photo illustration credit: University at Buffalo.

A new UB-led study suggests that chlorophyll-based nanoparticles are an effective imaging agent for the gut. The medical imaging drink, developed to diagnose and treat gastrointestinal illnesses, is made of concentrated chlorophyll, the pigment that makes spinach green. Photo illustration credit: University at Buffalo.

A July 11, 2016 University at Buffalo (UB) news release (also on EurekAlert) by Cory Nealon, which originated the news item, expands on the theme,

“Our work suggests that this spinach-like, nanoparticle juice can help doctors get a better look at what’s happening inside the stomach, intestines and other areas of the GI tract,” says Jonathan Lovell, PhD, assistant professor in the Department of Biomedical Engineering, a joint program between UB’s School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB, and the study’s corresponding author.

To examine the gastrointestinal tract, doctors typically use X-rays, magnetic resonance imaging or ultrasounds, but these techniques are limited with respect to safety, accessibility and lack of adequate contrast, respectively.

Doctors also perform endoscopies, in which a tiny camera attached to a thin tube is inserted into the patient’s body. While effective, this procedure is challenging to perform in the small intestine, and it can cause infections, tears and pose other risks.

The new study, which builds upon Lovell’s previous medical imaging research, is a collaboration between researchers at UB and the University of Wisconsin-Madison. It focuses on Chlorophyll a, a pigment found in spinach and other green vegetables that is essential to photosynthesis.

In the laboratory, researchers removed magnesium from Chlorophyll a, a process which alters the pigment’s chemical structure to form another edible compound called pheophytin. Pheophytin plays an important role in photosynthesis, acting as a gatekeeper that allows electrons from sunlight to enter plants.

Next, they dissolved pheophytin in a solution of soapy substances known as surfactants. The researchers were then able to remove nearly all of the surfactants, leaving nearly pure pheophytin nanoparticles.

The drink, when tested in mice, provided imaging of the gut in three modes: photoacoustic imaging, fluorescence imaging and positron emission tomography (PET). (For PET, the researchers added to the drink Copper-64, an isotope of the metal that, in small amounts, is harmless to the human body.)

Additional studies are needed, but the drink has commercial potential because it:

·         Works in different imaging techniques.

·         Moves stably through the gut.

·         And is naturally consumed in the human diet already.

In lab tests, mice excreted 100 percent of the drink in photoacoustic and fluorescence imaging, and nearly 93 percent after the PET test.

“The veggie juice allows for techniques that are not commonly used today by doctors for imaging the gut like photoacoustic, PET, and fluorescence,” Lovell says. “And part of the appeal is the safety of the juice.”

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

Surfactant-Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging by Yumiao Zhang, Depeng Wang, Shreya Goel, Boyang Sun, Upendra Chitgupi, Jumin Geng, Haiyan Sun, Todd E. Barnhart, Weibo Cai, Jun Xia, and Jonathan F. Lovell. Advanced Materials DOI: 10.1002/adma.201602373 Version of Record online: 11 JUL 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Single molecule nanogold-based probe for photoacoustic Imaging and SERS biosensing

As I understand it, the big deal is that A*STAR (Singapore’s Agency for Science, Rechnology and Research) scientists have found a way to make a single molecule probe do the work of a two-molecule probe when imaging tumours. From a July 29, 2015 news item on Nanowerk (Note: A link has been removed),

An organic dye that can light up cancer cells for two powerful imaging techniques providing complementary diagnostic information has been developed and successfully tested in mice by A*STAR researchers (“Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS Biosensing”).

A July 29, 2015 A*STAR news release, which originated the news item, describes the currently used multimodal imaging technique and provides details about the new single molecule technique,

Imaging tumors is vitally important for cancer research, but each imaging technique has its own limitations for studying cancer in living organisms. To overcome the limitations of individual techniques, researchers typically employ a combination of various imaging methods — a practice known as multimodal imaging. In this way, they can obtain complementary information and hence a more complete picture of cancer.

Two very effective methods for imaging tumors are photoacoustic imaging and surface-enhanced Raman scattering (SERS). Photoacoustic imaging can image deep tissue with a good resolution, whereas SERS detects miniscule amounts of a target molecule. To simultaneously use both photoacoustic imaging and SERS, a probe must produce signals for both imaging modalities.

In multimodal imaging, researchers typically combine probes for each imaging modality into a single two-molecule probe. However, the teams of Malini Olivo at the A*STAR Singapore Bioimaging Consortium and Bin Liu at the A*STAR Institute of Materials Research and Engineering, along with overseas collaborator Ben Zhong Tang from the Hong Kong University of Science and Technology, adopted a different approach — they developed single-molecule probes that can be used for both photoacoustic imaging and SERS. The probes are based on organic cyanine dyes that absorb near-infrared light, which has the advantage of being able to deeply penetrate tissue, enabling tumors deep within the body to be imaged.

Once the team had verified that the probes worked for both imaging modalities, they optimized the performances of the probes by adding gold nanoparticles to them to amplify the SERS signal and by encapsulating them in the polymer polyethylene glycol to stabilize their structures.

The researchers then deployed these optimized probes in live mice. By functionalizing the probes with an antibody that recognizes a tumor cell-surface protein, they were able to use them to target tumors. The scientists found that, in photoacoustic imaging, the tumor-targeted probes produced signals that were roughly three times stronger than those of unmodified probes. Using SERS, the team was also able to monitor the concentrations of the probes in the tumor, spleen and liver in real time with a high degree of sensitivity.

U. S. Dinish, a senior scientist in Olivo’s group, recalls the team’s “surprise at the sensitivity and potential of the nanoconstruct.” He anticipates that the probe could be used to guide surgical removal of tumors.

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

Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS Biosensing by U. S. Dinish, Zhegang Song, Chris Jun Hui Ho, Ghayathri Balasundaram, Amalina Binte Ebrahim Attia, Xianmao Lu, Ben Zhong Tang, Bin Liu, and Malini Olivo. Advanced Functional Materials, Vol 25 Issue 15
pages 2316–2325, April 15, 2015 DOI: 10.1002/adfm.201404341 Article first published online: 11 MAR 2015

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

This paper is behind a paywall.

A nanoparticle for a medical imaging machine that doesn’t exist yet

Researchers at the University of Buffalo (New York state) have created a nanoparticle that can be detected by six imaging devices according to a Jan. 20, 2015 news item on ScienceDaily,

It’s technology so advanced that the machine capable of using it doesn’t yet exist.

Using two biocompatible parts, University at Buffalo researchers and their colleagues have designed a nanoparticle that can be detected by six medical imaging techniques:

• computed tomography (CT) scanning;

• positron emission tomography (PET) scanning;

• photoacoustic imaging;

• fluorescence imaging;

• upconversion imaging; and

• Cerenkov luminescence imaging.

The advantages are obvious should somebody, somewhere create a hexamodal (aka, multimodal, aka hypmodal) sensing device capable of exploiting the advantages of this nanoparticle as the researchers hope.

A Jan. 20, 2015 University of Buffalo news release (also on EurekAlert) by Charlotte Hsu, which originated the news item, describes the ideas underlying the research,

This kind of “hypermodal” imaging — if it came to fruition — would give doctors a much clearer picture of patients’ organs and tissues than a single method alone could provide. It could help medical professionals diagnose disease and identify the boundaries of tumors.

“This nanoparticle may open the door for new ‘hypermodal’ imaging systems that allow a lot of new information to be obtained using just one contrast agent,” says researcher Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Once such systems are developed, a patient could theoretically go in for one scan with one machine instead of multiple scans with multiple machines.”

When Lovell and colleagues used the nanoparticles to examine the lymph nodes of mice, they found that CT and PET scans provided the deepest tissue penetration, while the photoacoustic imaging showed blood vessel details that the first two techniques missed.

Differences like these mean doctors can get a much clearer picture of what’s happening inside the body by merging the results of multiple modalities.

A machine capable of performing all six imaging techniques at once has not yet been invented, to Lovell’s knowledge, but he and his coauthors hope that discoveries like theirs will spur development of such technology.

The news release also offers a description of the nanoparticles,

The researchers designed the nanoparticles from two components: An “upconversion” core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.

Each part has unique characteristics that make it ideal for certain types of imaging.

The core, initially designed for upconversion imaging, is made from sodium, ytterbium, fluorine, yttrium and thulium. The ytterbium is dense in electrons — a property that facilitates detection by CT scans.

The PoP wrapper has biophotonic qualities that make it a great match for fluorescence and photoacoustic imagining. The PoP layer also is adept at attracting copper, which is used in PET and Cerenkov luminescence imaging.

“Combining these two biocompatible components into a single nanoparticle could give tomorrow’s doctors a powerful, new tool for medical imaging,” says Prasad, also a SUNY Distinguished Professor of chemistry, physics, medicine and electrical engineering at UB. “More studies would have to be done to determine whether the nanoparticle is safe to use for such purposes, but it does not contain toxic metals such as cadmium that are known to pose potential risks and found in some other nanoparticles.”

“Another advantage of this core/shell imaging contrast agent is that it could enable biomedical imaging at multiple scales, from single-molecule to cell imaging, as well as from vascular and organ imaging to whole-body bioimaging,” Chen adds. “These broad, potential capabilities are due to a plurality of optical, photoacoustic and radionuclide imaging abilities that the agent possesses.”

Lovell says the next step in the research is to explore additional uses for the technology.

For example, it might be possible to attach a targeting molecule to the PoP surface that would enable cancer cells to take up the particles, something that photoacoustic and fluorescence imaging can detect due to the properties of the smart PoP coating. This would enable doctors to better see where tumors begin and end, Lovell says.

The researchers have provided two images,

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core. Credit: Jonathan Lovell

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.
Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging. Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging.
Credit: Jonathan Lovell

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

Hexamodal Imaging with Porphyrin-Phospholipid-Coated Upconversion Nanoparticles by James Rieffel, Feng Chen, Jeesu Kim, Guanying Chen, Wei Shao, Shuai Shao, Upendra Chitgupi, Reinier Hernandez, Stephen A. Graves, Robert J. Nickles, Paras N. Prasad, Chulhong Kim, Weibo Cai, and Jonathan F. Lovell. Advanced Materials DOI: 10.1002/adma.201404739 Article first published online: 14 JAN 2015

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

This article is behind a paywall.