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Materials (Basel). 2019 Dec 09;12(24). doi: 10.3390/ma12244110.

Photoactive Pore Matrix for In Situ Delivery of a Photosensitizer in Vascular Smooth Muscle Cells Selective PDT.

Materials (Basel, Switzerland)

Magdalena Wawrzyńska, Maciej Duda, Iwona Hołowacz, Aleksandra Kaczorowska, Agnieszka Ulatowska-Jarża, Igor Buzalewicz, Wojciech Kałas, Edyta Wysokińska, Dariusz Biały, Halina Podbielska, Marta Kopaczyńska

Affiliations

  1. Department of Emergency Medical Service, Wroclaw Medical University, Parkowa 34, 51-616 Wroclaw, Poland.
  2. Department of Biomedical Engineering, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
  3. Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114 Wroclaw, Poland.
  4. Department and Clinic of Cardiology, Wroclaw Medical University, Borowska 213, 50-556 Wroc?aw, Poland.

PMID: 31818025 PMCID: PMC6947284 DOI: 10.3390/ma12244110

Abstract

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. 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. 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. The FTIR spectroscopic analysis confirmed that all studied matrices have been successfully functionalized with the target photosensitizers. Atomic force microscopy revealed that resulting photoactive matrices were very smooth, which can limit the implantation damage and reduce the risk of restenosis. No viability loss of human peripheral blood lymphocytes and no erythrocyte hemolysis upon prolonged incubations on matrices indicated good biocompatibility of designed materials. 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). It was demonstrated that 2 h incubation on the silica matrices was sufficient for uptake of the encapsulated photosensitizers. 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. 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. Presented data clearly demonstrate that porous silica-based matrices are capable of in situ delivery of photosensitizer for PDT of VSMC.

Keywords: ROS production; cardiovascular stent; intravascular photodynamic therapy; photoactive matrix; porous drug delivery system; restenosis; silica-based matrix

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