International Academic Cooperation

Project ‘International Academic Cooperation: Metallated Phthalocyanines as Highly Effective Photosensitisers for Cancer Phototherapy’

The project is implemented within a joint collaboration between the Laboratory for Bio and Chemoinformatics (HSE University–St Petersburg) and the Key Laboratory of Photonanomedicine and Experimental Therapeutics (Jiaxing University Medical College).

Project Objectives

Research objectives:

1) to identify and annotate (systematically summarise) small-molecule inhibitors of proteins mediating the heat-shock response and proteotoxic stress after PDT.

2) to select five inhibitors for each cell-survival signalling pathway and demonstrate their interactions with the corresponding targets using molecular dynamics and computational molecular modelling.

3) to provide in vitro evidence of inhibitors’ pharmacodynamic efficacy to improve therapeutic outcomes. Achieving these milestones will provide a basis for subsequent in vivo proof-of-concept studies.

Educational objectives:

Joint scientific seminars and international exchanges will be organised in the form of internships in the participating laboratories. Undergraduate and graduate students will be able to observe advanced computational workflows on server hardware and the subsequent analysis of results.

Applied objectives:

All deliverables related to formulations (eg, active compounds encapsulated in nanoparticles) will fall under intellectual property and will be evaluated through commercialisation pathways after the relevant studies (pharmacokinetics, pharmacodynamics, toxicology) are completed.

Project Tasks

(a) to build and computationally validate the structures of zinc phthalocyanine (ZnPC) and aluminium phthalocyanine (AlPC).

(b) to perform molecular dynamics simulations of ZnPC and AlPC in an explicit-solvent model.

(c) to model, separately, monomeric ZnPC and AlPC interactions in liposomes (represented as a membrane), LDL, and HDL to determine thermodynamic equilibria in each environment.

(d) to model, separately, monomeric ZnPC and AlPC interactions with albumin to determine thermodynamic equilibria in each environment.

(e) to model the effect of the coordinated metal on thermodynamic equilibrium in model bilayers of dipalmitoylphosphatidylcholine (DPPC) and in an aqueous environment; to perform computational tests of intramembrane stability of phthalocyanines coordinated with Zn and Al.

(f) in model bilayers and aqueous media, to calculate the (de)stabilising effect of phospholipid acyl-chain length on ZnPC and AlPC.

(g) to determine the effect of polyethylene glycol conjugated with DSPE on photosensitiser thermodynamic equilibria in DPPC bilayers and in the most stable bilayer.

(h) to model the effect of albumin in the extraliposomal space to determine whether albumin extracts ZnPC from the membrane.

(i) to model the effect of low-density lipoproteins (LDL) in the extraliposomal space in a lipid bilayer to determine ZnPC’s capacity to diffuse from the membrane into LDL.

(j) to model the effect of high-density lipoproteins (HDL) in the extraliposomal space in a lipid bilayer to determine ZnPC’s capacity to diffuse from the membrane into HDL.

(k) to provide recommendations for experiments in the partner laboratory and compare computational results with in vitro experimental findings.

Project Affiliation

Important!
Only publications (article and review types) in scientific journals included in Lists A, B, C, and D are considered, provided they do not have acknowledgments of other funding sources by authors affiliated with HSE University.

Affiliation with the university:

In Russian: Национальный исследовательский университет «Высшая школа экономики»

In English: HSE University / National Research University Higher School of Economics

Example acknowledgement of the funding source for a research output within which a publication is prepared:

In Russian: Статья/монография/глава подготовлена в ходе/в результате проведения исследования/работы в рамках проекта «Международное академическое сотрудничество» НИУ ВШЭ.

In English: The article/review was prepared within the framework of the HSE University ‘International Academic Cooperation’ project.

Project page with linked publications