Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers

Project Information

PHOTOCYLINDER

Grant agreement ID: 844145

DOI

10.3030/844145

Project closed

EC signature date 12 April 2019

Start date 8 July 2019

End date 2 September 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 224 933,76

EU contribution

€ 224 933,76

Coordinated by

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Periodic Reporting for period 1 - PHOTOCYLINDER (Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers)

Reporting period: 2019-07-08 to 2021-07-07

Summary of the context and overall objectives of the project

Final Report Summary- PHOTOCYLINDER (Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers)

Reporting period: 2019-09-03 to 2021-09-02

PHOTOCYLINDER project was aimed to accomplish two principal objectives: (1) Synthesis of novel Photo cylinders (2) Evaluation of the efficiency of the photo cylinder to bind to DNA 3-way junction and their photodynamic potential in cancer cells. In order to achieve these objectives research project was divided into work packages (details are provided in following sections). The first objective of this research has been successfully achieved. We have synthesized and characterized two new photo cylinders. With the newly designed photo cylinders we have evaluated the ability of the photo cylinders to bind DNA 3-way junctions. We found that these cylinders did not form DNA 3-way Junctions. In order to achieve second objective of the project we established a new collaboration with Prof. Palin at the School of Dentistry, University of Birmingham. We studied the photocytotoxicity and cellular localization and uptake of the cylinders in Sarcoma osteogenic -2 cell lines.

Substantial time was lost due to university closure during the COVID crisis. During this period, a research project was developed for SARS- CoV-2 inhibition and the work was performed as soon as lab reopen. The result was published in Angew Chem.

Another interesting variation of the PHOTOCYLINDER is the new method for the synthesis of Ru nano cylinder to increase the yield by 5 times with a simpler reaction protocol even without using any chromatographic separation technique.

Dissemination of the results: The project fellow collaborated with two of the post-graduate students from the host group and published a paper as a co-author in JACS (J. Am. Chem. Soc., 2020, 142, 20651-20660) and Angew Chem (Angew Chem Int Ed Engl. 2021, 60, 18144-1815.). We expect that at least 1 additional paper will come out in near future.

Conclusions: The MC Fellowship has offered the necessary support and funding for the development of photo cylinder chemistry using supramolecular nano cylinder as preliminary construct. The work has generated different photo cylinders and their photo activity has been evaluated in cancer cells. The preparation of the manuscript is underway and soon it will be submitted for publication. Developing newer method for synthesis of nano cylinder was another interesting variation during this project. These interesting synthetic methodologies will help to further explore them as drug candidates and offers several future options for other potential applications.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

PHOTOCYLINDER project was aimed to accomplish two principal objectives: (1) Synthesis of novel Photo cylinders (2) Evaluation of the efficiency of the photo cylinder to bind to DNA 3-way junction and their photodynamic potential in cancer cells. The first objective of this research has been successfully achieved and two new photo cylinders were synthesized and characterized. With the newly designed photo cylinders we then evaluated the ability of the photo cylinders to bind DNA 3-way junctions. We found that these initial photocylinders did not efficiently bind DNA 3-way Junctions due to the connectivity of the units. To achieve the second objective of the project we established a new collaboration with Prof. Palin at the School of Dentistry, University of Birmingham. We studied the photocytotoxicity and cellular localization and uptake of the cylinders in Sarcoma osteogenic -2 cell lines.

Substantial time was lost due to university closure during the COVID crisis. During this period, a research project was developed for SARS- CoV-2 inhibition and the work was performed as soon as lab reopen. The result was published in Angew Chem.

Dissemination of the results: The project fellow published two papers as a co-author in JACS (J. Am. Chem. Soc., 2020, 142, 20651-20660) and Angew Chem (Angew Chem Int Ed Engl. 2021, 60, 18144-1815.) in collaboration with post-graduate students from the host group. We anticipate at least 1 additional paper will result.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The MC Fellowship has offered the necessary support and funding for the development of photocylinder chemistry using supramolecular nanocylinders as a preliminary construct and for the fellow to gain a suite of new skills and expertises in supramolecular and bioinorganic design and synthesis, in biophysical DNA binding studies, and in in cellulo photodegradation studies. The work has generated different photo cylinders and their photo activity has been evaluated in cancer cells and two high impact (IF>10) publications have already resulted. New methods for synthesis of nano cylinders were also developed. These interesting synthetic methodologies will help to further explore them as drug candidates and offers several future options for other potential applications.

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