H2020Индивидуална стипендия2018–2020

ORTHOCAT · Bioorthogonal Photocatalytic Activation of Metal-Based Prodrugs

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-09-10 → 2020-09-09
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Златни наночастици ще транспортират витамин B2 и неактивни платинени лекарства, които се активират в тумора чрез синя светлина. Този метод цели да намали страничните ефекти при химиотерапията, като лекарството действа само в целевата зона.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Bioorthogonal Photocatalytic Activation of Metal-Based Prodrugs

Anticancer treatments frequently result in undesired side effects with high impact in the life quality of chemotherapy patients. One approach to minimize this effect is administrating an inactive version of the drug (prodrug) and converting it into the active drug directly, and only, in the tumor area. One of the ways to perform drug activation is by irradiating the prodrug with light. We recently discovered that riboflavin (vitamin B2) irradiated with blue light facilitates the transformation of platinum prodrugs intro cisplatin, one of the most used anticancer drugs in the clinics. Such flavin-mediated reaction is catalytic and occurs with high selectivity even in complex biological environments (i.e. bioorthogonality). The objectives of ORTHOCAT is to develop a system containing the different components (platinum prodrug and flavin) capable to perform this transformation as a single unit in cells and result in anticancer activity with low side effects. We would employ gold nanoparticles as vehicles to carry all the catalysis components.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

New cancer care methodologies with fewer side effects and no need for major surgery are required to enhance patient wellbeing. Photodynamic Therapy (PDT) partially accomplishes such mission employing light and a photosensitizer. Nevertheless, the PDT mechanism of action intimately depends on oxygen, which limits its efficacy, particularly in hypoxic solid tumours. Promising strategies to improve the impact of PDT in the clinics currently involve the design of photoactivatable transition metal complexes, a class of compounds which combines the rich photochemistry of metal complexes with the vast background of metal-based drugs in cancer therapy.In this framework, ORTHOCAT proposes an original and multidisciplinary strategy to exploit the efficiency and selectivity of riboflavin as unconventional photocatalyst for the activation of Pt(IV) anticancer prodrugs (Chem. Sci. 2017, 8, 4619). The project aims at designing novel riboflavin-based catalytic systems capable of activating Pt(IV) anticancer prodrugs inside the mitochondria of tumour cells. In particular, I will use triphenylphosphonium targeting vectors to develop new photocatalytic prodrug systems and delivery nanoplatforms which selectively accumulate in the mitochondria. Once in the organelle, riboflavin will act as singlet oxygen photosensitizer for PDT and simultaneously as photocatalyst to generate Pt(II) species for targeting mitochondrial DNA (photochemotherapy). Imbalance of mitochondrial delicate redox homeostasis by ORTHOCAT dual agents can trigger cell death through convenient cellular pathways. Therefore, ORTHOCAT prodrug systems will synergistically kill cancer cells with increased effectiveness, while potentially reducing side effects of metal-based drugs. Successful outcome of the project has the potential to deliver innovative therapeutic agents for cancer photochemotherapy.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACION DONOSTIA INTERNATIONAL PHYSICS CENTER · Donostia San SebastianКоординаторИспания