NANOPORATION

Ultrasound activiated nanoencapsulated targetted drug delivery and tumous cell poration

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 Obiettivo del progetto (Objective)

'Clinical drug delivery (DD) remains a problem of heightened industrial and academic interest. The proposed partnership seeks to embrace the problem by exploiting the unique expertise-base spanning the industrial research and academic pratners. We will provide inter-sectoral training of mulit-disciplinary researchers and create a novel new DD modality that addresses the key critical needs for non-invasive therapy via intelligent generic targeting and with intrinsic flexibility in drug choice. An essential simplicity to the present approach is that it takes strands of intrinsically safe technologies, and marries these into a powerful amalgam that offers true power and enhanced versatility. Chief amongst the areas of research are: (i) A generic encapsulating technology [CapsuTech - industrial partner] that will vector active anti-cancer drugs to a tumour target; (ii) Remotely triggered drug release on demand by externally focused ultrasound energy [development by industrial partner Insightec](iii) Enhanced drug uptake through the parallel disruption of cell membranes by the action of ultrasound on commercially available microscopic bubbles [sonoporation - University of Dundee]. The Dundee Group, who will lead this partnership, has made significant inroads to fundamental understanding with this latter strand. Moreover, the partners have gone to great lengths to factor in a level of training that also embraces existing trends for image guided intervention: in particular with magnetic resonance imaging (MRI). The project objectives we have realized are fully compatible with MRI technology and indeed, this prescience endows the overall scheme with significant added value. We anticipate that this synergistic and intra-sectoral multi-disciplinary research partnership will create significant momentum, enduring relationships, visionary researchers and a roadmap towards significant European market share, as well as delivering on truly excellent scientific objectives.'

Introduzione (Teaser)

Ultrasound for accurate drug delivery

Descrizione progetto (Article)

Conventional chemotherapy uses toxic chemical substances that damage rapidly dividing cells, a characteristic of cancer cells. These substances can permeate the whole body and can also damage healthy.

The EU-funded 'Ultrasound activated nano-encapsulated targeted drug delivery and tumour cell poration' (NANOPORATION) project focused on new methods of directed drug delivery exclusively to tumours. Objectives included the development of a new treatment, whereby reduced dosage of existing anti-cancer drugs is achieved with more effective tumour cell uptake.

Researchers optimised nano-drug carriers to improve specific encapsulation properties for different anti-cancer drugs: Doxorubicin, Taxol, Camptothecin and Mitoxantrone. The results of optimisation were verified thorough in vitro release under hyperthermia and sonication conditions. The final kinetics study in vivo was performed by ultrasound under magnetic resonance (MR) imaging guidance.

In vitro experiments have carried out for researching the kinetics of uptake of the drugs by human carcinoma cell lines (MCF7, A375M, PANC-1, PC-3 and KB). Cytotoxicity was measured using standard techniques and the separation of thermal and mechanical (bubble-mediated) effects were investigated.protocols were explored using in vivo mouse models. The scientists monitored immune-compromised mice with human xenograft tumours (colon carcinoma HCT116) to measure tumour growth rate. MR imaging in vivo verified the best MRI parameters.

To encourage and strengthen the transfer of knowledge, two summer schools were organised during the project. Five publications presented project results and NANOPORATION has been widely recognised in the international community.

The project has proved that using the developed technique, anti-cancer substances in nano-capsules could be delivered only when focused ultrasound is applied. This reduces the potential harmful side effects of chemotherapy and increases its efficacy which may lead to higher survival rates and enhanced quality of life for patients.