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Photoacoustic in vivo imaging with near infrared-dye doped nanoparticles to further develop by a reasearch/technical agreement

Country of Origin: Germany
Reference Number: TODE20181113002
Publication Date: 27 November 2018

Summary

A German research organization and a Dutch company are developing novel nanoparticle (NP) based imaging technology for medical diagnostics, including pre- and intra-operativ tumor diagnostics. NP labeled tumors can be non-invasive and non-ionizing localized. Intra-operative control enables precise resection of tumor, without damage of surrounding healthy tissue. The technology should be further developed with clinical or industrial partners based on a research or technical cooperation agreement.

Description

A German research organization which is responsible for the nanoparticle (NP) development and a Dutch company in charge of the development of the pre-clinical imaging technique are developing novel NP based imaging technology for medical diagnostics. 
In most cases, conservative cancer treatment is the surgical removal of the primary tumor combined with radiation or chemotherapy. Such interventions are usually invasive, and often damage a big part of healthy tissue. This leads to a high physical stress and reduced life quality of patients after surgery. Additionally, the occurrence of recurrences or metastases could not be prevented if the tumor tissue is not completely removed. The development of new highly efficient tumor diagnostic strategies can considerably increase the chances of cure, simplify the therapy and reduce potential damages. This would result in an improvement of the patients´ living condition while simultaneously reducing the cost.
Photoacoustic (PA) imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. It combines the sensitivity and contrast of optical imaging with the depth and high resolution of our ultrasound technology. Usually, organic dyes and gold nanoparticles (NPs) can be used as a contrast agent for PA imaging. Organic dyes are commonly sensitive to photobleaching and decompose fast in vivo, what diminishes their applicability as a marker in diagnostic tests. Gold NPs are non-biodegradible. Interest in the new contrast agent is particularly extensive.
These problems can be overcome by integrating dye molecules into nanocarrier. Dye doped NPs exhibit the optical properties of the embedded fluorophores, and are adapted to given environmental conditions thanks to the matrix material. The incorporation offers many advantages. First, a large number of fluorophores can be encapsulated inside a single NP, which increases the optical signal intensity. Second, NP matrix can protect doped dyes from photobleaching by minimizing the influence of oxygen and enabling the fluorescence to be constant, which creates accurate measurement conditions. Since several years, the German research institute is continuously developing near infrared (NIR) dyes doped nanoparticles (NPs) on basis of liposomes and mesoporous silica NPs. Depending on the synthesis parameters, the size of NPs can be adjusted in the range of 100 – 150 nm. The choice of silica and liposomes as a NP-matrix is motivated by their high biocompatibility, biodegradability and the possibility of surface modifications. They can be used as delivery systems for dyes and drugs and contribute to the stabilization of these compounds in vivo. The great potential of dye doped silica NP as a contrast agent for photoacoustic (PA) pre-clinical and clinical imaging could already be shown by the industrial project partner (Netherlands) in vitro and in vivo. By comparison with the pure dyes, encapsulated dyes reveals a clear increase of optical signal intensity and long-term stability (almost no bleaching effects).
The two partners are looking for an industrial or clinical partner cooperation in order to further develop our the technology within a collaboration project e.g. EU-funded. Desired outcome of the partnership could be multimodal photoacoustic and ultrasound imaging method, which offers real-time co-registration of the ultrasound image and photoacoustic images for nanoparticle based contrast agents.
The main goal of the present project is to develop a new monitoring feature supporting the diagnosis and treatment of intracorporal tumors by PA imaging using NIR-dye doped NPs - In vivo optical tumor marker for surgery.

Advantages and Innovations

Innovation and attractiveness of the planned solution lies in the combination of smart diagnostic approach and targeted therapy. NP labeled tumors can be non-invasive and non-ionizing localized. Additional, intra-operative control enables precise resection of tumor, without damage of surrounding healthy tissue. Besides exogenous contrast agents, also endogenous contrast agents (e.g. oxygenated/deoxygenated hemoglobin, melanin etc.) can be visualized in real-time and unmixed together in the same image/data. These are crucial features and more beneficial than other image modalities, as in other image modalities there would be an increased exogenous influence on the subject when aiming for the same amount of tissue information. The plan is to get more data and information out of the tissue with less exogenous penetration.
Moreover, the planned approach aims for a solution which reduces the use of lab animals and further:
- It gives the ability to test in vitro with a tissue mimicking phantom (three dimensional in vitro test systems, reconstruction of body similar conditions).
- The configuration of the system allows the refining of specifications.
- The offered technology avoids the need for surgery, or damage to critical organs (Image guided injection).
- It is characterized by a high throughput.
- It is a translational technology.

Stage Of Development

Available for demonstration

Requested partner

Profile of desired partner:
1) Manufacturers of (nano-) particles with the focus on nanoparticles for preclinical / clinical applications (diagnostics, therapy, drug delivery)
2) Manufacturers of organic dyes with the focus on dyes for biomedical applications
3) Research organizations with the focus on the production of medical products (contrast agents, pharmaceutical formulations etc.
4) Research groups from clinics with the focus on preclinical and medical imaging, diagnostics

Project tasks of desired partner:
1) Optimization of nanoparticle and nanoparticle formulations
2) Active contribution to the development of contrast agents
3) In-vivo and in-vitro testing of new developed nanoparticles, contrast agents, imaging technologies
4) Future support in distribution and networking

Cooperation offer ist closed for requests