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New generation products for photodynamic therapy of tumors

Patented microcrystalized hydrophobic phtalocyanine liposomal drug form plus nayf4 (dopped by yb and er) nanoparticle drug form with matching lasers will be developed, converting 980 nm to 670 nm and enabling unlimited light penetration for infrared pdt curing tumors/metastases in any location.

Very little penetration of visible light (~ 2 cm with rapidly decreasing energy) through the human skin and tissues presents a significant barrier for widespread use of photodynamic therapy (PDT) for treatment of malignant tumors . This barrier might be overcome by light sources in the near infrared region of 800 to 1000 nm, which still does not match water absorption (> 1000 nm). Therefore, the main aim of this project will be TO CREATE A NEW SYSTEM OF UPCONVERSION OF NANOPARTICLES AND MODIFY THEIR SURFACE WITH A POLYMER SHELL CONTAINING PDT DRUG - HYDROXYALUMINUM PHTHALOCYANINE (PC) IN ORDER TO CONVERT NEAR INFRARED 980 nm RADIATION TO 670 nm FOR EXCITATION OF PC. The PC liposomal drug formulation will be also developed upon its pharmaceutically-suitable form by directed microcrystalization of PC crystals free of free of Al-empty molecules which interfere with the curing effect upon PDT. Moreover, the new nanoparticle drug formulation will be developed and prepared on the basis of the recrystalized hydrophobic PC using NaYF4 nanoparticles (dopped by Yb and Er creating the upconversion effect) with two, one nonporous and one porous shell PC. If successful, this new revolutionary drug formulation will enable PDT by 980 nm light which possesses an unlimited penetration through the human body and allow its use for practically any tumor location and would also allow curing of metastases. The resulting infrared PDT will provide a cheap alternative to extremely costly therapies for cancer, such as proton therapy and other radiation therapies. Lanthanide-ion doped NaYF4 upconverting nanoparticles (UCNs), which are capable of converting long wavelength near-infrared radiation to shorter wavelength through an upconversion process, are attractive alternatives to overcome problems associated with low penetration. However, there are still two primary challenges: (1) energy losses resulting from the process of fluorescent resonant energy transfer between nanoparticles and coated dyes, and/or cross-relaxation of a variety of doped lanthanide ions, (2) difficulties in tuning different-color upconversion fluorescences in a facile and general way in nanoparticles of homogeneous composition. Our strategy will account for the above obstacles and will develop Yb3+/Er3+ doped NaYF4 nanoparticles, adjust Yb3+, Er3+ as well as Na content in NaYF4 mixed crystals and optimize temperature and procedure of nanoparticle preparation in order to maximize 976 nm absorption and 670 nm upconversion fluorescence. Moreover, this will be precisely matched with coherent 980 light sources developed by the Eureka partners. The constructed coherent ligth sources of 980 nm will provide cheaper alternatives to devices used in the demonstration of proof of principle (already with positive results) , e.g. such as femtosecond Chameleon (Coherent Inc.) laser. Phtalocyanine- NaYF4 nanoparticle drug formulations (both intravenous and topical) will be tested on selected human tumors xenotransplanted to nude mice and on mice with deeply localized tumors in the more mature stage of the project. These tests will enable refined adjustment of both drug formulation (testing photophysics of upconversion in the Inst. Physiology, nanoparticles tumor targeting, adjustment of light sources for upconversion in cooperation with EUREKA partners, etc.) and light sources for infrared PDT. The project is expected to develop nanoparticle drug formulation for infrared PDT into preclinical stage plus in parallel to develop microcrystalized PC liposomal drug formulation into the clinical testing stage. Guarantor of the clinical testing will be Czech company Wake, experienced for own healing gel, HemaGel®, for which Wake obtained FDA approval in teh USA besides registration in EU countries besides Czech Republic. Having successfully introduced into market a healing gel, new challenge for Wake company is to introduce into the market PDT PC liposomal gel and in the future nanoparticle PC drug formulations. Moreover, besides a simple laser source of 980 nm, a optical tomograph is planned to be developed by Medistellar and Kvant companies, Eureka partners, to locate and focuse several suboptimal 980 light beams (not harming penetrating tissue) into one spot in precisely define xyz coordinates to deliver dense and powerful light energy into the site of tumor or metastase to be cured. If successful, the companies could obtain position of the market leaders in this laser technology. The project will thus develop a classic topical preparation for PDT which enables very short drug to light time interval of 10 min (cf. Czech patent No.298978 and PCT CZ2007/000107 and EU patent pending) with a compelte set of laser light sources plus one revolutionary nanoparticle drug formulation for intravenous application at infrared PDT with another compelte set of laser light sources. This will enable to spread PDT into common medical praxis as efficient and cheap alternative.
Acronym: 
PDT NANO
Project ID: 
8 020
Start date: 
01-01-2013
Project Duration: 
48months
Project costs: 
1 320 000.00€
Technological Area: 
Cytology, Cancerology, Oncology
Market Area: 
Other therapeutic (including defibrillators)

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