Project description
Blue light-controlled drug-releasing implants
The inability to use high-energy blue/UV light as the signal for light-triggered on-demand drug delivery is due to a formidable physiological barrier. This makes red light the only alternative. However, red light has intrinsically lower energy and limited value in photochemical reactions because the photocleavage of covalent bonds typically requires UV light. The EU-funded PADRE project will use blue/UV light to trigger and precisely control on-demand drug-releasing implants. The project will use light generated through photon upconversion or integrated light sources. The first method will allow pioneering, effective red-to-blue/UV triplet-triplet annihilation upconversion in a hydrogel environment. The second will enable light generation by a co-implanted light source.
Objective
This proposal introduces a next-generation platform for next generation optimally personalised drug therapy: on-demand drug releasing implants triggered and controlled by blue/UV light. The technology is based on novel light generation pathways and a light-sensitive nanocellulose drug reservoir.
A formidable physiological barrier for light-triggered drug release has been the inability to use high-energy blue/UV light as the triggering signal. This is because the penetration depth of light drops to from a few cm to under 100 micrometers when moving from near-infrared to UV light, making deeper targets within tissues accessible only to red light. However, red light, with its intrinsically lower energy, has limited value in photochemical reactions because the photocleavage of covalent bonds typically requires UV-light. This is why many groups are looking at e.g. red-to-blue photon upconversion strategies. The major objective in PADRE is to circumvent the issue of unavailable blue light in implants through local light generation. Having access to light with higher energy will enable a much wider chemical toolbox, including photocleavable linkers.
I will use blue/UV light to trigger and precisely control drug release. The approach creates an unconventional way to modulate the release profiles without unwanted drug leakage. The light will be generated through either 1) photon upconversion, or 2) integrated light sources. With the first approach, I will pioneer efficient red-to-blue/UV triplet-triplet annihilation upconversion in a hydrogel environment, while in the second approach I will generate light by a co-implanted light source. Both approaches are feasible according to my preliminary results on efficient triplet-triplet annihilation upconversion and photoresponsive liposomes and will be demonstrated in a working implant prototype. The core breakthrough of PADRE will be a viable solution to employ blue excitation in precisely-tailored drug-releasing implants.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
00014 Helsingin Yliopisto
Finland