H2020Индивидуална стипендия2018–2020

CylcoRu4PACT · Cyclometallated ruthenium complexes for photo-activated chemotherapy

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

Период: 2018-04-01 → 2020-03-31
Финансиране от ЕС: 165 599 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Рутениеви комплекси се тестват като лекарства, които се активират от червена светлина за унищожаване на ракови клетки, например при рак на кожата. Това помага за по-прецизно насочване на токсичността към тумора, без да се увреждат здравите клетки.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Cyclometallated ruthenium complexes for photo-activated chemotherapy

In chemotherapy the primary question is that of the selectivity of the drug, as the toxicity of the compound should affect only the tumour, not the healthy cells. Selective activation of a prodrug by an external signal such as light has appeared as a promising alternative to biological targeting, as it allows for delivery of the toxicity of the compound with great spatial and time selectivity. The optimal wavelengths for activating prodrugs in vivo is the region where light penetration is maximal, i.e., in the red region of the spectrum. The results obtained in this project represent a significant contribution to the design and development of new photoactivated drugs. Namely, in the literautre, cyclometallated ruthenium complexes absorb in the red region of the spectrum but they cannot be activated with such light. Compounds synthesized in this project not only absorbs in the red region of the spectrum, but also they exchange a ligand upon red light irradiation. One of the compounds prepared in this project showed twice higher toxicity towards A431 (skin cancer) cells after red light irradiation. The main problem of the complexes studied in this project is their low thermal stability in the dark and their insolubility in water. Follow-up research is now taking place to introduce ligands that improve the dark stability and water solubility of these complexes. With these improvements, new complexes will be at hand that will show much higher light-induced toxicity in vitro and can be further tested in animal models. Overall, the present project has opened new prospects for the design of light-activated anticancer drugs.

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

Цел на проекта

Chemotherapy is efficient in curing cancer, but most treatments are very hard to stand for the patient, and side effects limit treatment efficacy. Phototherapy is a promising alternative, where the toxicity of a light-sensitive chemotherapeutic compound is locally released upon visible light irradiation of the compound-containing tumour. Photodynamic therapy is already available in the clinic for oxygen-rich tumours; however, it fails when the oxygen concentration at the place of irradiation is too low. In this project I propose to synthesize new ruthenium-based photochemotherapeutic compounds containing cyclometallated ligand, and to test them in an in vitro model of hypoxic cancer. The presence of a carbon-metal bond is known to shift the light absorption properties of ruthenium polypyridyl complexes towards the photodynamic window, a wavelength range where light penetrates optimally into biological tissues. However, cyclometallation usually quenches the ligand photosubstitution properties of ruthenium compounds because it strongly modifies the energy of their excited states. In this project, I will introduce sterically hindering groups on the cyclometallated ligand to recover photoreactivity of the complexes while keeping light absorption at high wavelengths. The challenges of this project consist on the one hand in achieving efficient ligand photosubstitution reactions with cyclometallated ruthenium compounds, and on the other hand in minimizing the cytotoxicity in the dark while maximizing cytotoxicity after red light irradiation at low oxygen concentrations. The ruthenium prodrugs will be synthesized, their photochemical properties will be measured, and their cytotoxicity against human cancer cell lines will be determined in an in vitro model of hypoxic cancer. This project will set new grounds in the treatment of hypoxic tumours and propose a new way to overcome side effects occurring in traditional anticancer chemotherapy.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITEIT LEIDEN · LeidenКоординаторНидерландия