NANOPHOTO

Targeted Nanosystems for Improving Photodynamic Therapy and Diagnosis of Cancer

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 Obiettivo del progetto (Objective)

'The overall objective of this proposal is the development of one or more nanosystems loaded with Foscan® and conjugated to cancer cell specific ligands for improving the efficacy and selectivity of photodynamic therapy (PDT) and optimise a fluorescence-based tumour imaging approach. At present, PDT with Foscan® can be very effective but is not selective because Foscan® accumulates in the tumour tissue as well as in healthy ones. A great improvement of the therapy can only come from the availability of a carrier able to seek cancer cells and deliver Foscan® selectively to them. Three types of nanosystems, namely, liposomes, silica nanoparticles or poly(lactide-co-glycolide) copolymer nanoparticles, have been selected as potential nanocarriers for the selective delivery of Foscan®. The selection was mainly based on the different chemical nature of these systems, which can affect biocompatibility. During the first part of the project each type of nanosystem will be optimised through in vitro and in vivo tests and leader nanocarriers will be selected and conjugated to cancer cells specific ligands for increasing the selective delivery of Foscan®. The ligands we will use (folic acid, EGF, and antibodies) for targeting the nanosystems find their corresponding receptor over-expressed on the surface of cancer cells, therefore allowing a selective delivery of drugs in these cells. In vitro and in vivo investigations will be carried to demonstrate the validity of our approach and deliver, at project conclusion, a final product which can then be tested clinically. Because of the red fluorescence emitted by Foscan®, once it is selectively accumulated in cancer cells fluorescence based technique can be used for tumour imaging and diagnosis. Therefore we expect to develop a Foscan® loaded nanosystem/s which can be used for improving both therapeutic and tumour imaging approaches.'

Introduzione (Teaser)

A new drug-delivery formulation has been developed to improve photodynamic therapy for cancer treatments. It reduces the number of side effects while offering patients a better quality of life after treatment.

Descrizione progetto (Article)

In photodynamic therapy (PDT), cancer cells are first made sensitive to a particular type of light using a photosensitising drug. When the resulting sensitised cells are exposed to light of a specific wavelength, they produce a form of oxygen that kills nearby cancer cells.

Targeting cancer cells more specifically and reducing the side effects of PDT are two problems associated with this therapy. With this in mind, the 'Targeted nanosystems for improving photodynamic therapy and diagnosis of cancer' (Nanophoto) project was established. The main objective of this EU-funded project was to engineer nano-scale carriers.

The aim of these nanocarriers was to direct the delivery of a photosensitising drug selectively to cancer cells. The project team studied three potential nanosystems for entrapping the drug, all of which proved successful.

However, a challenge for the Nanophoto team was that the nanoparticles carrying the drug still had to evade the body's formidable defence mechanisms. So, the researchers coated the nanocarriers with a layer of polyethylene glycol to obtain nanoparticles with the ability to escape recognition and capture by white blood cells, i.e. stealth particles.

In tumour-bearing rats using the new formulation, tests showed that there was a threefold increase in drug uptake in the cancer cells, as compared to the standard formulation. In addition, the dosage of the drug could be lowered by 20?% while preserving the same therapeutic effect as that of the standard formulation. This result is particularly important for reducing the adverse side effects of PDT.

In conclusion, Nanophoto's studies showed that the new formulation substantially improves the treatment of cancer with PDT. Based on this finding, a project partner is planning to start the European drug approval procedure and to schedule clinical trials with the new formulation for delivering the PDT drug.