Advanced theranostic approach in cancer
combining photodynamic therapy and nanoparticles
M-Era.Net Topic 5 “Tailoring of bioactive material surfaces for health applications”
01.07.2016 – 30.06.2019
Coordinator: Lisbon University – Prof. Luis Filipe Vieira Ferreira
Partner 2: “Victor Babes” National Institute of Pathology, ROMANIA
Prof. Mihail Eugen Hinescu
Partner 3: “Carol Davila” University of Medicine and Pharmacy, ROMANIA
Prof. Rica Boscencu
Partner 4:Institute of Physical Chemistry, Romanian Academy, ROMANIA
Dr. Radu Petre Socoteanu
Partner 5: Autonomous University of Madrid, SPAIN
Prof. Antonio CUADRADO
Small and Medium Enterprises
Partner 6: SC Biotehnos SA
Dr. Laura OLARIU
Partner 7: DOKUMAR
Prof. Selma Huveyda Basaga
University of Lisbon https://www.ulisboa.pt/en/
“Victor Babeș” National Institute of Pathology http://www.ivb.ro/
University of Medicine and Parmacy “Carol Davila” http://www.umf.ro/
Institute of Physical Chemistry, Romanian Academy http://www.icf.ro/
SC BIOTEHNOS SA http://www.biotehnos.com/
Theranostic is an emerging medical concept, combining imagistic diagnosis and therapy for personalized medicine. Considering the need for highly targeted therapy in cancer, the main objectives of the project are: 1) to develop new tools for one step imaging and therapy directed towards tumors (theranostic approach). Taking advantage of the huge biomedical potential and versatility of nanoparticles (NPs) and of fluorescent porphyrins as photosensitizers (PSs), we will bring improved joint power by designing, producing and characterizing porphyrin/biopolymer-coated iron oxide NPs, exhibiting superior imaging and photodynamic properties in solid tumors; 2) to test the hypothesis that inhibition of the antioxidant response of targeted tumors for developing a co-therapy can increases the efficacy of nano-PDT. Secondary objectives: 1) to build a multidisciplinary network in the field of nanotheranostics; 2) to train and to sustain career development for young researchers; 3) to obtain scientific and economic advantages for partner institutions, both academia and SMEs.
The project is in line with the M-era.Net topic “Tailoring of bioactive material surfaces for health applications” by developing a new/improved (nano)solution with multi-functional properties for theranostics in cancer. It will be demonstrated at preclinical level (in vitro and in animal models), addressing both therapeutic efficacy and toxicological issues. We will start the project at TLR 1 – basic principles observed, advancing through TRL 2 – technology concept formulated, and TRL 3 – experimental proof of concept, towards TRL 4 – technology validated in lab, at the end of the project.
The project is proposed by a multidisciplinary consortium composed of 3 universities, 2 research institutes and 2 SMEs from Portugal, Spain, Turkey and Romania. Partners will benefit from high level joint research and will share state-of-the-art technologies and know-how.
Activities will be organized in 8 WPs: WP1-Porphyrins, WP2-Nanoparticles and nanosystems, WP3-Structural characterization of nanosystems, WP4 Photochemical characterization of nanosystems, WP5-Preclinical study, WP6-Mechanistic study, WP7-Dissemination and technology transfer, WP8-Management.
Main deliverables: 1) Porphyrinic compounds and biocompatible functionalized nanosystems with anti-tumor activity and acceptable side-effects, comprehensively characterized from the physicochemical, photophysical and preclinical points of view; 2) therapeutic targets for improving photodynamic therapy by modulating the antioxidant response; 3) technical specifications and procedures for all the investigated compounds / nanostructures; 4) study-specific biobank, that will further allow the consortium to continue research beyond the project’s frame; 5) improved protocols for preclinical investigation of nanostructures; 6) patent request documentation (at least 1); 7) documentation for pre-registering of at least 2 porphyrinic compounds at the European Chemicals Agency; 8) publications in high impact journals (at least 6) and result communication at relevant international congresses (at least 10); 9) training and exchange of young scientists in the field of nanotechnology and experimental medicine (at least 8); 10) organization of at least 2 workshops (industry showcase).
The market strategy is to patent at least 1 nanosystem and to promote the patent to the pharmaceutical/nanotechnology industries after project completion.
The new nanosystems and technologies which will be generated by the current project represent the premise for a future large-scale project joining pharmaceutical/nanotechnology industry and academic research. Additionally, this project represents a good opportunity for young researchers to get specialized and to grow in a competitive research area. The success of the project is supported by the recognized expertise of the participating scientists, their previous fruitful cooperation and the commitment to apply material science for developing biomedical applications.
Main objectives: 1) development of new/improved theranostic agent(s) for one-step imagistic diagnosis and targeted therapy in cancer: functionalized iron oxide NPs coated with new PDT-active porphyrins, and conditioned with polymers; 2) development of a new PDT-based therapeutic strategy using the proposed theranostic agent, and pharmacological modulation of the endogenous antioxidant system as co-therapy for improved PDT.
Secondary objectives: 1) Setup of a functional multidisciplinary consortium in the field of nanomedicine for further joining large international networks in the field; 2) Knowledge dissemination by patents, high impact publications and communications, for increasing our international visibility and for promoting results towards industry; 3) Training and career development for the next-generation of researchers.
- At least two new photoactivable porphyrinic compounds exhibiting improved photodynamic properties compared to those exhibited by commercialy available porphyrinic photosensitizers like Foscan, Fospeg, Foslip, Photochlor
- At least one biocompatible NS (polymer-coated magnetic NPs with porphyrinic compounds attached) displaying anti-cancer activity and acceptable side-effects in tumor-bearing small laboratory animals
- Molecular networks underlying the anti-cancer activity of the lead NS
- Molecular targets for adjuvant therapy to improve PDT in solid tumors by modulation of the antioxidant response
- Study-specific biobank to be used by consortium partners after completion of the current study, for advancing the mechanistic studies using next-generation technologies
- Technical specifications and procedures for all the investigated compounds / nanostructures
- Improved protocols specific for preclinical investigation of nanostructures
- Documentation for at least 1 patent request on the lead NS, submitted to the Romanian Patent and Trademark Office, and documentation for pre-registering of 2 porphyrinic compounds at the European Chemicals Agency
- Detailed commercialization strategy
- At least 6 publications in high impact journals (we take into consideration that patent-associated results should not be previously published) and At least 10 communications at relevant national and international congresses in the field of cancer biology and therapeutics, immunology, redox biology, etc
- Knowledge exchange visits for young researchers (at least 2 exchange visits per country team)
- At least two workshops organized at the end of the project for presenting project outcomes to academia, clinicians, producers of nanosystems for medical use, pharmaceutical companies and regulatory authorities in the field of nanomedicines and nanosafety
- Web page for promoting knowledge generated in the project towards specialists and the general public.
Work package list:
|WP no.||Work package title||Main content
|WP1||Porphyrins||Synthesis and functionalization of porphyrins||45||Rica Boscencu (UMFCD)||ICF, UL|
|WP2||Nanoparticles and nanosystems||In silico modeling, synthesis of nanoparticles and nanosystems development||50||Luis Ferreira (UL)||UMFCD, ICF|
|WP3||Structural characterization of nanosystems||Size distribution, crystalline structure, morphology, elemental composition, surface area||24||Radu Socoteanu (ICF)||UL|
|WP4||Photophysical characterization of nanosystems||Photochemical and photophysical characterization, luminescence, singlet oxygen generation under light irradiation||42||Luis Ferreira (UL)||ICF|
|WP5||Preclinical study||In vitro study, in vivo study on animal models of cancer: biodistribution, anti-tumor activity, toxicological profile||70||Gina Manda (IVB)||UAM, BTH, UMFCD|
|WP6||Mechanistic study||Molecular mechanisms, , oxidative activity and antioxidant response, modulation of Nrf2 transcription factor||65||Antonio Cuadrado (UAM)||IVB, BTH, UMFCD|
|WP7||Dissemination and technology transfer||Patent(s), publications, communications, knowledge and technology exchange||43||Huveyda Basaga (DMR)||All partners|
|WP8||Management||Global coordination, working groups, information flow, ethical issues||36||Luis Ferreira (UL)||All partners|