Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: In Vitro Evaluation

Abstract

with subsequent damage to the cell components and consequent cell death. [1] PDT can be used to target tumor cells and is typically utilized in a combination therapy regime, together with other modalities such as radiotherapy, chemotherapy, and surgery. To optimize cell damage in the tumor and prevent significant collateral damage to healthy cells, the PS should be specifically localized in the pathogenic region. The lifetime and mean diffusion lengths of different ROS are very variable and localization will ensure that illumination generates ROS close to, at the surface of, or inside malignant tumor cells.Of particular interest for development of efficient PDT systems are porphyrins because the photochemical and photophysical properties may be tuned through modification of the central metal ion (if present) or through peripheral substituents. [2][3][4][5] However, despite the great potential of porphyrins as photosensitizers, these compounds possess crucial limitations in terms of biomedical application [6,7] such as a high dark toxicity, rather low activity under physiological conditions and typically poor water solubility. Efficient strategies to overcome these limitations and at the same time harness the beneficial properties of porphyrins are the (bio)-conjugation of the porphyrin to natural or synthetic polymers [8][9][10][11] or their incorporation in biocompatible nano carriers. Nanocarriers suitable for PDT materials include organic and inorganic nanoparticles, [12][13][14][15][16][17] liposomes, [18][19][20][21] and block copolymer-based vesicles or micelles. [22][23][24] Synthetic vesicles with sizes in the nanometer range, so-called polymersomes, are particularly appealing as carriers because they can be prepared with desired properties, [25] such as biocompatibility, possess an inner cavity where water-soluble photosensitizers can be encapsulated, [26] membranes allowing the entrapment of a hydrophobic photosensitizer and exhibit improved mechanical stability and robustness compared to liposomes. [27] There are a few examples of porphyrin-incorporating polymersomes, mostly concerning the non-covalent loading of the hydrophobic membrane with water insoluble porphyrins. [11,[28][29][30][31][32][33] The aim of those studies was to use the photophysical properties of the porphyrins to improve in vivo imaging. We have previously reported the synthesis and characterization of a water soluble tetra-N-alkylpyridinioporphyrin tetrabromide (TPyCP) (Scheme 1) which efficiently generates singlet oxygen both free Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano-assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20-tetrakis(1-(6-ethoxy-6-oxohexyl)-4-pyridin-1-io)-21H,23H-porphyrin tetrabromide porphyrin is inserted into polymersomes in order ...

New buffer systems for photopainting of single biomolecules

“…84 Water soluble porphyrin is a wellknown ROS promoter, due to singlet oxygen formation. [85][86][87][88] In this work, we present new buffer systems for improved LAPAP patterning efficiency. We characterise the effect of Mn 2+ as well as ruthenium porphyrin (RuPo) on three fluorophore class representatives by optimizing buffer systems for single-molecule LAPAP.…”

Porphyrinic Metal–Organic Framework PCN-224 Nanoparticles for Colocalization of Nanoparticle-Cargo in the Skin and Enhancement of Sonodynamic Efficacy

“…11,12 When they are free in the solution, their ability to constantly produce ROS would be decreased with time. 13 In addition, because of their relatively large and complex structures, the skin delivery of porphyrins might be impeded by the natural barrier of the stratum corneum, 14 and their poor local accumulation in the impaired skin would also be a challenge for targeted delivery to the pathological sites within the skin. 15 To overcome these limitations, porphyrins have been commonly incorporated into various types of nanoparticles that can endow them with more powerful functions in SDT as well as PDT.…”

“…The efficiency of SDT is highly associated with sonosensitizers, most of which were porphyrin-based substances, such as hematoporphyrin and Photofrin. , Nevertheless, as organic small molecules, porphyrin and its derivatives generally suffer from low water solubility, low stability, poor selectivity, and rapid clearance in vivo. , When they are free in the solution, their ability to constantly produce ROS would be decreased with time . In addition, because of their relatively large and complex structures, the skin delivery of porphyrins might be impeded by the natural barrier of the stratum corneum, and their poor local accumulation in the impaired skin would also be a challenge for targeted delivery to the pathological sites within the skin .…”