The main role of PDT in the treatment of restenosis is to generate ROS that will interfere with SMC survival and consequent remodeling process. PDT involves a photosensitizing agent (PS) that accumulates selectively in the target cells and its illumination with a low-power laser light of an appropriate wavelength to generate cytotoxic reactive oxygen species (ROS).
Photodynamic therapy (PDT) was shown to modulate the vascular response to injury caused by PCI. Therefore, the new approach to design stents is needed with a rationale to block neointimal formation, while preserving endothelial function.
While modern DES successfully prevents neointimal proliferation, the presence of unspecific anti-proliferative drugs impairs the reendothelialization, which increases the risk of in-stent thrombosis. Moreover, the endothelial cells play an important role in the regulation of the vascular tone and inhibiting inflammation and thrombus formation. Although, blocking SMC proliferation is important for hindering intimal hyperplasia, sustained growth of endothelial cells (EC) is essential for successful vascular repair. DES elute antiproliferative drugs into the surrounding tissue, thus indiscriminately block vascular cells. Therefore, three generations of drug eluting stents (DES) stents were designed with the ability to block SMC proliferation. Proliferation and migration of tunica media layer (middle coat) smooth muscle cells (SMC) in response to the vascular wall injury, are essential events leading to the subsequent neointimal thickening, which eventually causes vessel narrowing. Percutaneous coronary interventions (PCI) involving stent implantation are routinely used for the treatment of coronary artery disease. Presented data clearly demonstrate that porous silica-based matrices are capable of in situ delivery of photosensitizer for PDT of VSMC. On the other hand, limited reactive oxygen species (ROS) induction in HUVECs in our experimental set up suggests that the proposed method of PDT may be less harmful for the endothelial cells and may decrease a risk of the restenosis. Moreover, the amount of the absorbed photosensitizer was sufficient for induction of a phototoxic reaction as shown by a rise of the reactive oxygen species in photosensitized VSMC. It was demonstrated that 2 h incubation on the silica matrices was sufficient for uptake of the encapsulated photosensitizers. The suitability of photoactive surfaces for PDT was tested in two cell lines relevant to stent implantation: vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMC). No viability loss of human peripheral blood lymphocytes and no erythrocyte hemolysis upon prolonged incubations on matrices indicated good biocompatibility of designed materials.
Atomic force microscopy revealed that resulting photoactive matrices were very smooth, which can limit the implantation damage and reduce the risk of restenosis. The FTIR spectroscopic analysis confirmed that all studied matrices have been successfully functionalized with the target photosensitizers. These matrices can be used for coating cardiovascular stents used for treatment of the coronary artery disease and enable intravascular photodynamic therapy (PDT), which can modulate the vascular response to injury caused by stent implantation-procedure that should be thought as an alternative for drug eluting stent. To demonstrate usability of this new material, three silica-based materials with different pore size distribution as a matrix for doping with Photolon (Ph) and Protoporphyrin IX (PPIX) photosensitizers, were prepared. In this study we present the porous silica-based material that can be used for in situ drug delivery, offering effective supply of active compounds regardless its water solubility.