Abstract
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 to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (1 O2 ) upon irradiation in vitro. The photoactivation of the free and polymersome-encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non-specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not-toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions.
Highlights
Making them suitable for application in photodynamic therapy
According to dynamic light scattering measurements (DLS) measurements and transmission electron microscopy (TEM) micrographs (Figure S1, Supporting Information) the obtained polymersomes had the shape of hollow spheres with hydrodynamic radii (Rh) around 100 nm (Figures S3 and S4, Supporting Information)
Www.mbs-journal.de reduces by 56% (15 min irradiation) and ends up at 1–2% after 60 min of irradiation. These viability assays indicate that our porphyrin loaded polymersomes reduce in vitro the cell viability in higher efficacy compared to similar results obtained by other studies with similar systems of porphyrin containing polymersome.[22,23]
Summary
TPyCP containing polymersomes were formed by self-assembly of the triblock copolymer PMOXA6-PDMS34-PMOXA6 in the presence of TPyCP using the film rehydration method.[38,41] According to DLS measurements and TEM micrographs (Figure S1, Supporting Information) the obtained polymersomes had the shape of hollow spheres with hydrodynamic radii (Rh) around 100 nm (Figures S3 and S4, Supporting Information). The thickness of the polymersome membrane is around 9.2 nm.[42] The polymersomes preserved their structural integrity after constant irradiation with red LED light compared with the non-irradiated polymersomes as observed by TEM micrographs (Figure 1). The integrity of the polymersomes under constant irradiation is further confirmed by DLS measurements taken. The unspecific uptake of the PS containing polymersomes and PS by mammalian cells is known and has been studied and optimized.[43] We know that the uptake takes place after 24 h incubation of the polymersomes with the cells and the final concentration range of the polymer is 0.25–0.1 mg mL−1. For this study we used the same experimental and concentration conditions to ensure the internalization of the compartments into the cells.[43,44,45]
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