Project R-11407

NEED - Bioresponsive nanocarriers as a therapy for cancer and wound healing. (Research)

In 2018, 710 235 new cases of head and neck squamous cell cancers (HNSCC) were diagnosed worldwide. Current treatments include surgery followed by radiotherapy (RT), and/or chemotherapy (CT). Nevertheless, the majority of patients with advanced stage HNSCC are inoperable. Besides, CT and RT cause a wide variety of side effects such as untreatable wounds. There is thus an urgent need for novel side-effect free therapies. This project aims to develop novel nanotherapeutic systems that (1) could offer a new, targeted treatment for HNSCC and (2) can cure RT-induced wounds. First, we will design a novel drug-loaded dual responsive core-shell nanocarrier system where the core and shell are independently triggered using respective biological cues such as reactive oxygen species (ROS), pH and glutathione (GSH), which are known to be upregulated in wounds and tumours. The nanocarrier can encapsulate various agents such as growth factors, therapeutics, and fluorescent dyes which are released upon the specific stimuli. Loading the particles with fluorescent dyes allows a detailed monitoring of ROS and GSH levels over time in the tumour and wound microenvironment, enabling to adjust the design for optimal responsiveness. Next, the nanocarrier system is loaded with a CT agnt and a photosensitizing agent and its effectiveness is evaluated in a mouse model of HNSCC. Alternatively, they are loaded with growth factors and anti-inflammatory agents and will be tested in a mouse wound healing model. This project will result in well-designed bioresponsive nanoparticles with high clinical applicability, setting the basis for clinical trials.

01 January 2021 - 31 December 2024