Engineered Near-infrared Light Sensitive Nanovesicles for Precise Image-Guided Thermally Triggered Cancer Therapy

Lead Research Organisation: University of Manchester
Department Name: School of Health Sciences

Abstract

Nanocarriers have demonstrated great potential to control collateral damage and improve biodistribution of a variety of chemotherapeutic agents. A phenomenon that is key to enable this performance improvement is the preferential accumulation of nanocarriers into a cancerous tissue due the hyperpermeability of its vasculature. However, the heterogeneous tumour distribution and drug release from nanocarriers is an issue.

Our aim is to solve the problem engineering multifunctional nanocarriers to combine real-time imaging and triggered release is highly required to achieve precise and efficient therapy. Temperature-responsive vesicles has been attracting increasing attention lately and these vesicular systems have found their way into the clinic (with Thermodox being the most advanced form). However, the heating technologies used to trigger drug release are all based on bulk heating of the tumour mass which has the limitation of uneven and sub-thermal heating.

Therefore, to overcome the shortcomings listed above, we propose the engineering of all-in-one image-guided and thermal responsive nano-vesicles that encapsulate anti-cancer drugs in their interior and labelled with light sensitive-clinically approved-indocyanine green (ICG) dye. The ICG near-infrared (NIR) absorbance is essential to allow deep tumour penetration and minimise light scattering. We have shown previously that external activation of ICG-labelled non-temperature sensitive vesicles allows non-invasive dynamic imaging of the distribution into the tumour.

In this project we hypothesize that the incorporation of ICG in the outer membrane of thermally triggered vesicles will not only allow the tracking the non-invasive distribution in the tumour mass, but also to transduce the absorbed light radiation by the dye molecules into local heat. The generation of photothermal heating at the nanoscale level in the outer membrane of temperature-sensitive vesicles is expected to be associated with more efficient thermally triggered drug release with less unwanted thermal damage.

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