A study of transport of photosensitizers for minimally invasive photodynamic therapy of cancers


Researchers from G.A. Krestov Institute of Solution Chemistry, Ivanovo State University of Chemistry and Technology, Belarusian State University of Informatics and Radioelectronics, National Medical Research Radiological Centre, and Ivanovo Region Clinical Hospital have studied the mechanisms of vascular transport of photosensitive drugs - photosensitizers (PS) that are applied in minimally invasive photodynamic therapy (PDT) of cancers.

Conventional methods of neoplasm treatment, such as chemo- and radiotherapy, are not always effective but often cause a lot of side effects because of the damage to healthy tissues. Photodynamic therapy (PDT) is recognized as one of the promising directions in treatment of localized tumours without negative after-effects. PDT is based on selective accumulation of photosensitizers in tumour tissues. Photosensitizers are substances that are activated by a specific wavelength of light energy to generate reactive oxygen species killing cancerous cells. Photodynamic therapy is often used to treat a great number of superficial tumours: basalioma, melanoma, as well as tumours of hollow organs: lungs, urinary bladder, esophagus or stomach. Intraoperative fluorescence diagnosis (PD) and PDT are widely applied for fluorescence navigation and PDT treatment of tumour bed and sentinel nodes.

Higher selectivity of drug accumulation in tumour cells is one of the key success factor of PDT. A lot of tumours have low-density lipoprotein (LDL) receptors on their surface, whereas repolarized immune cells - tumour-associated macrophages - mainly accumulate high-density lipoproteins (HDL). Albumin-transported photosensitizers are mainly accumulated in the vascular network of tumours. PS binding with low-density lipoproteins results in higher selectivity of drug accumulation in tumour cells and improves the PDT efficiency. The researchers have studied the interaction of a number of photosensitizers based on natural chlorophyll with blood plasma proteins by the gel filtration chromatography method.

In their study, they experimentally established that interaction with the transport proteins of blood is largely affected by charge, as well as the number and mutual position of charged groups in the photosensitizing molecule. For example, because of the difference in the charge location, one monocationic chlorin photosensitizer is transported by lipoproteins, whereas another one does not bind with the protein components of plasma at all. Anionic PS based on chlorin e6 are almost completely transported by the albumin fraction. The presence of several charged groups in the PS molecule levels off the affinity to lipoproteins, which are important as drug delivery agents that accumulate in the tumour cells. Introduction of passive delivery vehicles, such as Tween 80 or PVP, into a PS solution does not influence the PS distribution in the plasma proteins, which indicates strong binding of PS with the proteins. The researchers concluded that chlorins carrying one cationic group in a certain macrocycle position are more effective than anionic and polycationic macrocycles. They also showed that the application of one of such drugs - monocationic chlorin photosensitizer, 50% of which is transported by LDL - ensures complete recovery in 75% of rats with sarcoma after one photodynamic treatment procedure. The achieved effect is retained over the whole period of observation - 90 days in rats< which is equivalent to a 5-year period in humans.

For more details about the study go to: https://www.sciencedirect.com/science/article/abs/pii/S0167732223019220.