Periodic Reporting for period 1 - NANOCARGO (Photo/magnetic stimulated nanocargos for superior cancer treatments)
Berichtszeitraum: 2018-10-01 bis 2020-09-30
1.1 What is the problem being addressed by Nanocargo?
The disease targeted in Nanocargo is breast cancer (BC) which is considered as one of the most invasive and common cancers among women worldwide, affecting 2.1 mln female patients each year. Breast cancer is as well the leading cause of cancer death among European women, 1 in 8 women in the EU-28 will develop BC before the age of 85.
There have been significant advancements in the treatment of BC in recent years but the mortality rate remains still high. Nowadays a full removal of breast tissues (mastectomy) or partial mastectomy (lumpectomy) is considered as primary treatment. In advanced stages the adjuvant treatment merging chemotherapy, radiotherapy and hormonal/biological therapy is applied.
Within Nanocargo we developed a superior breast cancer therapy and diagnosis (theranostic) approach that destroys cancer cells inside the body without the need for painful surgery. For this purpose we use functionalized nanoparticles and enhance the effectiveness of therapy by combining photothermal therapy (PTT) and magnetic hyperthermia (MHT) with localized pharmacotherapy in a targeted and minimally invasive procedure.
1.2 Why Nanocargo' results are important for society?
According to the WHO data BC is not only the most frequent carcinoma among of female but also a cause of app. 15% of all cancer-related deaths. Around 1% of all patients are man, who are most often diagnosed at an advanced stage and thus usually have lower overall survival rates. European Cancer Information System statistics show that in 2018 the number of diagnosed BC incidents across EU was 405,000, with relevant number of deaths 98,000. ECIS predicts that this year the cancer burden will rise up to 2.7 mln new cases (data for 27 EU countries, both sex) with women breast cancer estimated to be most commonly diagnosed carcinoma at the level of 28,7%. Therefore effective breast cancer prevention, including extensive screening and early diagnosis, as well as development of new and dedicated cancer treatment strategies tailored to the individual needs of patients, is crucial to improve treatment outcomes.
1.3 What were the overall objectives of Nanocargo project?
The innovation developed within Nanocargo project met all the initially proposed scientific objectives. We developed the next generation personalized breast cancer treatment which uses few different therapeutic strategies at the same time and multiple imaging modalities for therapy monitoring. This synergistic approach provides a rapid, safe, and effective treatment and better visualization of tumor inside the body.
The disease targeted in Nanocargo is breast cancer (BC) which is considered as one of the most invasive and common cancers among women worldwide, affecting 2.1 mln female patients each year. Breast cancer is as well the leading cause of cancer death among European women, 1 in 8 women in the EU-28 will develop BC before the age of 85.
There have been significant advancements in the treatment of BC in recent years but the mortality rate remains still high. Nowadays a full removal of breast tissues (mastectomy) or partial mastectomy (lumpectomy) is considered as primary treatment. In advanced stages the adjuvant treatment merging chemotherapy, radiotherapy and hormonal/biological therapy is applied.
Within Nanocargo we developed a superior breast cancer therapy and diagnosis (theranostic) approach that destroys cancer cells inside the body without the need for painful surgery. For this purpose we use functionalized nanoparticles and enhance the effectiveness of therapy by combining photothermal therapy (PTT) and magnetic hyperthermia (MHT) with localized pharmacotherapy in a targeted and minimally invasive procedure.
1.2 Why Nanocargo' results are important for society?
According to the WHO data BC is not only the most frequent carcinoma among of female but also a cause of app. 15% of all cancer-related deaths. Around 1% of all patients are man, who are most often diagnosed at an advanced stage and thus usually have lower overall survival rates. European Cancer Information System statistics show that in 2018 the number of diagnosed BC incidents across EU was 405,000, with relevant number of deaths 98,000. ECIS predicts that this year the cancer burden will rise up to 2.7 mln new cases (data for 27 EU countries, both sex) with women breast cancer estimated to be most commonly diagnosed carcinoma at the level of 28,7%. Therefore effective breast cancer prevention, including extensive screening and early diagnosis, as well as development of new and dedicated cancer treatment strategies tailored to the individual needs of patients, is crucial to improve treatment outcomes.
1.3 What were the overall objectives of Nanocargo project?
The innovation developed within Nanocargo project met all the initially proposed scientific objectives. We developed the next generation personalized breast cancer treatment which uses few different therapeutic strategies at the same time and multiple imaging modalities for therapy monitoring. This synergistic approach provides a rapid, safe, and effective treatment and better visualization of tumor inside the body.
Whitin the Nanocargo project we have successfully achieved all Milestones, as well as completed all Deliverables. A unique four-steps method of photo-magnetic core shell nanocargos’ synthesis was first developed. Then the chemical process was extended by another 3 steps, in which we functionalized the nanocarriers with the anticancerous drug and cancer cell targeting aptamer. The binding of aptamer and drug on the core shell assembly was characterized at each intermediate step by fluorescence spectroscopy and UV-VIS spectroscopy.
Next, the biocompatibility, safety and clinical efficacy of the proposed nanosystem was demonstrated by in vivo, in vitro and ex vivo tests. First, stimuli-responsive drug release from nanocarriers in presence of alternating magnetic field was confirmed. Then the cell viability tests on non-cancerous L929 cells treated with HNC formulation (1000 μg/mL) showed that therapy is safe. The preliminary toxicological and histopathological tests on small animals didn’t show any signs of adverse effects. No indication of injuriousness and no organ related systemic toxicity was observed for the dosage of 2000 mg/kg. The effectiveness of HNCs was next validated on the breast cancer cell line MCF7. Almost 95-96% breast cancer cells were killed died after 24h of synergetic therapy. This strong anticancer therapeutic effect suggest that proposed HNCs can be successfully used as multi-modal therapeutic agents for BC treatment.
Nanocargo has been also very successful in terms of knowledge’ dissemination and educational activity. Within the project we:
- published 3 books, 6 book chapters and 7 scientific articles in high impact factor journals,
- delivered 11 conference lectures,
- given1 lecture to primary school students
- deliver 2 lectures to high school students
- deliver 3 lectures for the broad non-academic audience during Lower Silesian Science Festival
- given 7 presentations to promote H2020 programme & scientific cooperation outside Europe
- organized 2 on-line workshops together with Regional Contact Point in Wroclaw and Wroclaw Center for Technology Transfer
Next, the biocompatibility, safety and clinical efficacy of the proposed nanosystem was demonstrated by in vivo, in vitro and ex vivo tests. First, stimuli-responsive drug release from nanocarriers in presence of alternating magnetic field was confirmed. Then the cell viability tests on non-cancerous L929 cells treated with HNC formulation (1000 μg/mL) showed that therapy is safe. The preliminary toxicological and histopathological tests on small animals didn’t show any signs of adverse effects. No indication of injuriousness and no organ related systemic toxicity was observed for the dosage of 2000 mg/kg. The effectiveness of HNCs was next validated on the breast cancer cell line MCF7. Almost 95-96% breast cancer cells were killed died after 24h of synergetic therapy. This strong anticancer therapeutic effect suggest that proposed HNCs can be successfully used as multi-modal therapeutic agents for BC treatment.
Nanocargo has been also very successful in terms of knowledge’ dissemination and educational activity. Within the project we:
- published 3 books, 6 book chapters and 7 scientific articles in high impact factor journals,
- delivered 11 conference lectures,
- given1 lecture to primary school students
- deliver 2 lectures to high school students
- deliver 3 lectures for the broad non-academic audience during Lower Silesian Science Festival
- given 7 presentations to promote H2020 programme & scientific cooperation outside Europe
- organized 2 on-line workshops together with Regional Contact Point in Wroclaw and Wroclaw Center for Technology Transfer
3.1 Detailed innovation description and its progress beyond the state of the art
Our innovation proposes the unique solution that enhance a therapy’ efficiency by conjugating magneto-plasmonic nanoparticles with biologically active and therapeutic agents into a multifunctional hybrid nanocarriers (HNC). Our nanostructures are synthesized in a unique way and provide a single nanoplatform that may at the same time (1) recognize and target a cancer cells in a smart way, (2) deliver the therapeutic drug directly to tumor, (3) use simultaneously 3 complementary therapeutic strategies, such as PTT, MHT and targeted pharmacotherapy, and (4) few diagnostic methods to monitor therapy’ outcomes in real-time. The proposed procedure is minimally invasive, increases the visibility of cancer in multiple imaging modalities and provides a drug release inside the tumor in controlled way, at the right time and dosage needed for a patient. The developed invention is protected by the patent application No EP20192433.9 submitted to the European Patent Office.
3.2 Potential impacts of the innovation
The nonotheranostic system developed within Nanocargo project is considered as one of the crucial R&D innovations, that can revolutionize the breast cancer market by combining an effective and personalized treatment with real-time imaging diagnostics. The innovation has been already identified by European Commission as having high potential and awarded the prestigious Grand Prix Innovation Radar Prize in 2020.
The current effectiveness of cancer therapy depends on the efficient delivery of cytostatic drug and killing the cancer cells without recurring. Classic chemotherapy has serious drawbacks, such as lack of specificity, harmful toxic effects on healthy organs and usually poor bioavailability due to highly hydrophobic nature of therapeutics. Also the chemical resistance of tumor cells reduces the treatment outcomes,
Our innovations overcame all above limitations and may have high socio-economical impact. The BC market is currently rising fast due to increasing incidences of cancer cases and growing patients awareness. However, the high expenditure in the treatment is still a significant restrain factor. In 2018, the global BC market was valued at USD 19.0 bln with CAGR 10.6% and it is estimated that by 2026 will reach USD 40.5 bln. The maximum revenue is now generated by targeted therapy segment, which accounts over 70% market share and is predicted to have the fastest growth by 2026. This emphasis the significance of the new, cost-effective, rapid, patient-tailored and multimodal BC R&D initiatives, such as the one proposed by Nanocargo project.
Our innovation proposes the unique solution that enhance a therapy’ efficiency by conjugating magneto-plasmonic nanoparticles with biologically active and therapeutic agents into a multifunctional hybrid nanocarriers (HNC). Our nanostructures are synthesized in a unique way and provide a single nanoplatform that may at the same time (1) recognize and target a cancer cells in a smart way, (2) deliver the therapeutic drug directly to tumor, (3) use simultaneously 3 complementary therapeutic strategies, such as PTT, MHT and targeted pharmacotherapy, and (4) few diagnostic methods to monitor therapy’ outcomes in real-time. The proposed procedure is minimally invasive, increases the visibility of cancer in multiple imaging modalities and provides a drug release inside the tumor in controlled way, at the right time and dosage needed for a patient. The developed invention is protected by the patent application No EP20192433.9 submitted to the European Patent Office.
3.2 Potential impacts of the innovation
The nonotheranostic system developed within Nanocargo project is considered as one of the crucial R&D innovations, that can revolutionize the breast cancer market by combining an effective and personalized treatment with real-time imaging diagnostics. The innovation has been already identified by European Commission as having high potential and awarded the prestigious Grand Prix Innovation Radar Prize in 2020.
The current effectiveness of cancer therapy depends on the efficient delivery of cytostatic drug and killing the cancer cells without recurring. Classic chemotherapy has serious drawbacks, such as lack of specificity, harmful toxic effects on healthy organs and usually poor bioavailability due to highly hydrophobic nature of therapeutics. Also the chemical resistance of tumor cells reduces the treatment outcomes,
Our innovations overcame all above limitations and may have high socio-economical impact. The BC market is currently rising fast due to increasing incidences of cancer cases and growing patients awareness. However, the high expenditure in the treatment is still a significant restrain factor. In 2018, the global BC market was valued at USD 19.0 bln with CAGR 10.6% and it is estimated that by 2026 will reach USD 40.5 bln. The maximum revenue is now generated by targeted therapy segment, which accounts over 70% market share and is predicted to have the fastest growth by 2026. This emphasis the significance of the new, cost-effective, rapid, patient-tailored and multimodal BC R&D initiatives, such as the one proposed by Nanocargo project.