Controlled Delivery of Extracellular ROS Based on Hematoporphyrin-Incorporated Polyurethane Film for Enhanced Proliferation of Endothelial Cells

Abstract

The principle of photodynamic treatment (PDT) involves the administration of photosensitizer (PS) at diseased tissues, followed by light irradiation to produce reactive oxygen species (ROS). In cells, a moderate increase in ROS plays an important role as signaling molecule to promote cell proliferation, whereas a severe increase of ROS causes cell damage. Previous studies have shown that low levels of ROS stimulate cell growth through PS drugs-treating PDT and nonthermal plasma treatment. However, these methods have side effects which are associated with low tissue selectivity and remaining of PS residues. To overcome such shortcomings, we designed hematoporphyrin-incorporated polyurethane (PU) film induced generation of extracellular ROS with singlet oxygen and free radicals. The film can easily control ROS production rate by regulating several parameters including light dose, PS dose. Also, its use facilitates targeted delivery of ROS to the specific lesion. Our study demonstrated that extracellular ROS could induce the formation of intracellular ROS. In vascular endothelial cells, a moderated increase in intracellular ROS also stimulated cell proliferation and cell cycle progression by accurate control of optimum levels of ROS with hematoporphyrin-incorporated polymer films. This modulation of cellular growth is expected to be an effective strategy for the design of next-generation PDT.

Study of Singlet Oxygen Dynamics on Silicon Polymer Matrix

“…Despite the advantages, the applications of singlet oxygen-induced by the photoexcited photosensitizer have some other problems with the additional pollution of the photosensitizers themselves and unintended reactions with nonspecific materials. To solve the problems in the applications, various photofunctional materials that included photosensitizers are developed by many researchers [7–12]. Among them, recently, the studies have reported the bactericidal and the cell proliferation effects with the photofunctional polymers that isolate photosensitizer insides of the polymer matrix, which may provide the solution of the problems previously described.…”

Main Active Components and Cell Cycle Regulation Mechanism of Astragali Radix and Angelicae Sinensis Radix in the Treatment of Ox-LDL-Induced HUVECs Injury and Inhibition of Their Cell Cycle

“…Therefore, ROS are considered to be signaling molecules that lead to endothelial dysfunction during the development of AS. Ox-LDL plays an essential role in the early stages of AS by inhibiting cell proliferation, promoting inflammation, and inducing the apoptosis of endothelial cells [ 15 , 16 ]. Excessive ROS levels can lead to the apoptosis or necrosis of endothelial cells by causing irreversible damage to the DNA, proteins, RNA, and other biological molecules.…”

“…Excessive ROS levels can lead to the apoptosis or necrosis of endothelial cells by causing irreversible damage to the DNA, proteins, RNA, and other biological molecules. Previous studies have shown that ROS affect cell proliferation and differentiation by directly or indirectly regulating the transcription of genes encoding cell signaling-related factors [ 15 ]. LDH, which mediates cell survival, can be considered an indicator of the degree of cell membrane damage.…”

Recent Advances in ROS-Responsive Cell Sheet Techniques for Tissue Engineering

“…However, increasing of intracellular ROS up to a threshold level delays cell adhesion to ECM proteins, and results in a negative function of PTP on FA development and cytoskeleton organization. We previously found that extracellular ROS increase the amount of intracellular ROS [79]. H 2 O 2 can diffuse through specific aquaporins (AQP) in the plasma membrane, and superoxide anion (O 2 – ) can penetrate the cell membrane through anion channels (Cl – channel-3) to initiate intracellular signal transduction [79,80,81,82].…”

“…We previously found that extracellular ROS increase the amount of intracellular ROS [79]. H 2 O 2 can diffuse through specific aquaporins (AQP) in the plasma membrane, and superoxide anion (O 2 – ) can penetrate the cell membrane through anion channels (Cl – channel-3) to initiate intracellular signal transduction [79,80,81,82]. There are many ways in which extracellular ROS can be transported into cells, but the exact mechanism of ROS that affects cell detachment is unknown.…”