H2020Индивидуална стипендия2018–2020

NIRCOThera · Spatiotemporal, near-infrared light controlled carbon monoxide delivery for cancer immunotherapy

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

Период: 2018-03-01 → 2020-02-29
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Въглеродни нанотръби се използват за пренасяне на лекарства като доксорубицин и въглероден моноксид, които се активират в тумора чрез инфрачервена светлина. Този метод помага за повишаване на концентрацията на активните вещества в болните клетки и намаляване на токсичното действие върху здравите тъкани.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Spatiotemporal, near-infrared light controlled carbon monoxide delivery for cancer immunotherapy

The success of advanced cancer diagnosis and treatment relies on the localized enrichment of drugs or imaging agents at tumour sites. The technologies enable targeted delivery and on-demand activation represent an excellent solution to the issue in the battle of cancer. The tumour-targeted delivery and on-demand activation of prodrugs could enhance the concentration of active drugs selectively at tumour sites while sparing the exposure of toxic drugs to normal tissues, alleviating the adverse drug effects. There are several methodologies for on-demand activation. Among them, the light-responsive release, especially with near-infrared light of better tissue penetration depth and biocompatibility, provides a high degree of spatiotemporal precision. Also, bioorthogonal click-to-release reactions have been rapidly emerging in recent years because of its bioorthogonality and controlled bond-cleavage. The objective of this research is to develop a novel cargo delivery avenue, enabling controlled prodrug release, e.g. the immunomodulatory molecule carbon monoxide (CO) and the chemotherapy drug doxorubicin, exclusively at tumour sites with spatiotemporal precision. The strategy proposed consists of single-walled carbon nanotubes (SWCNTs) and the prodrug cargos. The strategy will enable spatiotemporal control over prodrug activation via integrating the tumour-targeting property of SWCNTs, the stability and non-toxicity of the small molecule prodrugs and the on-demand activation of prodrugs at tumour sites. Besides, the lipid functionalized SWCNTs have shown biocompatibility, ultrahigh tumour uptake and relatively fast clearance and excretion from the health tissues, which impart the platform promising for in vivo application. The biocompatibility of the nanotool, the stability of the prodrug and the active drug release profile would be evaluated, followed by its dose- and time-dependent therapeutic potential on tumour treatment. We expect that this novel on-demand prodrug activation platform would enable significant improvements to the existing cancer treatment regimes in the near future.

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

Цел на проекта

Carbon monoxide (CO) is a gaseous signaling molecule naturally produced by the human body. In recent years, CO has shown its anti-inflammatory and immunomodulatory properties and thus therapeutic potential in the treatment of inflammatory disorders and cardiovascular diseases. It is promising to exploit the modulatory effect of exogeneous CO in tumour microenvironment where inflammation and angiogenesis are the critical components of tumour progression and metastasis, which is largely unexploited. For this purpose, it is key to manipulate CO exposure in a precise dose and time-controlled manner exclusively at the tumour site. Herein, we propose to develop a new CO delivery avenue, enabling controlled CO release to tumour sites with spatiotemporal precision by using near infrared light (NIR). Specifically, the strategy consists of single-walled carbon nanotubes (SWCNTs) loaded with CO releasing molecules (CORMs). We have reported the development of a SWCNTs-based bifunctional system that enables intratumoural protein delivery and NIR activation, which is ready to be applied to realize controlled CO release in vivo. We plan to conjugate [ReBr3(CO)3][NEt4]2 to SWCNTs. The rhenium complex is chosen because of its stability and non-toxicity while the lipid functionalized SWCNTs have shown biocompatibility, ultrahigh tumour uptake and relatively fast clearance and excretion from the health tissues, which impart the platform promising for in vivo application. We will evaluate the stability of the platform, followed by the NIR-triggered CO release profile and then dose- and time-dependent effect on both cancer cells and tumour-infiltrating immune cells, including the generation of reactive oxygen species (ROS) and expression of multiple genes associated with tumour progress. Furthermore, expecting increased cancer cell sensitivity to chemotherapeutics with CO treatment, we will combine the proposed strategy with current chemotherapy to eradicate tumours in animal models.

Оригинален текст от CORDIS (на английски).

Участници

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство