Cancer is one of the most common diseases with around 20 million new cases per year worldwide. According to WHO, in 2020, 10 million deaths occurred due to different cancer diseases, leading to an immense health issue with rising socio-economic costs due to increasing number of patients each year.
Cancer therapy is not always successful with the current available drugs on the market. Furthermore, available therapies can result in severe side effects which compromise the patient´s quality of life. Therefore, there is a need for improved cancer treatments.
Photodynamic therapy (PDT) is a clinically approved and minimally invasive treatment with the benefit of very few side-effects compared to other cancer therapeutics, such as chemotherapy and radiation treatments. PDT’s therapeutic approach relies on a light-activated photosensitizer (PS), ideally completely inactive in the dark state, and a light source to selectively kill abnormal cells. With these compounds, clinicians can achieve high control of where and when the compound will be activated. The principle of PDT is that exposure of a PS to light in the presence of cellular oxygen generates reactive oxygen species (ROS) and causes irreparable damage to cellular molecules resulting in selective destruction of the tumour.
PDT has emerged as a promising tool in oncology, and it is clinically approved to treat several different cancer types including neck, head, skin, and prostate cancer, as well as actinic keratosis, a type of precancerous skin disease caused by UV exposure. In addition to treating cancer diseases, PDT is used in the treatment of other diseases. For instance, in ophthalmology, PDT is used to treat eye diseases including, polypoidal choroidal vasculopathy (abnormally shaped vessels in the choroid under retina) or central serous chorioretinopathy (fluid accumulates under the retina). Both cause loss of vision for the patients.
A current limitation of PDT is the short lifetime of singlet oxygen which restricts its diffusion distance in cells resulting in lowered efficiency of PDT. However, strategies devoted to the design of highly selective organelle-targeted PSs have been shown to overcome this limitation and improved the PDT effect. Furthermore, less ideal PSs i.e., the heavy atom-based PSs can be toxic even in dark and may therefore cause genomic instability when they are accumulated in organelles such as the nucleus indicating the urgency of developing new generation of PSs with novel mechanisms of action.
Our unique solution is a new heavy atom-free PS that targets DNA structures in pre-exosomal vesicles and not the nuclei. Synthesis of our molecule is non-expensive and relatively fast, easy and straightforward. Furthermore, our PS is non-toxic at high concentrations in the dark and toxic only upon light-activation. When light-activated, our PS is very potent at low concentrations in both in vitro and in vivo which will vastly contribute to potential significant decrease of side-effects.