Design of a Stimulus‐responsive Human Serum Albumin‐based Nanoparticle for Photodynamic Therapy (LB249)
The FASEB Journal(2014)
Abstract
Photodynamic therapy (PDT) is a promising treatment for cancer. It relies on the accumulation of a photosensitizer (PS) drug in the target area and the subsequent irradiation with a light source to induce the formation of reactive oxygen species that cause cell death. The incorporation of these drugs in drug delivery systems (DDS) has proven to increase selectivity and overall efficiency of the therapy in vivo. We have synthesized a new DDS using human serum albumin nanoparticles (HSA NPs) of a discrete size as carriers. The PS drug Chlorin e6, which has proven to be effective for PDT, was covalently linked onto the NPs to prevent non‐selective release. Our NPs were stabilized with a redox‐sensitive crosslinker for targeted activation of the drug in a reducing environment, such as that of the cell cytoplasm. Absorbance and fluorescence spectroscopy experiments showed that the NPs disintegrated and that the PS photoquenching decreased in a 10 mM glutathione solution, resulting in the activation of the drug. The system was physically characterized in terms of size, shape and drug loading. The size obtained (280‐300 nm) was appropriate for accumulation in cancer tissue. Cell internalization and phototoxicity of the system were tested in HeLa cells by cell viability assays and confocal microscopy, showing efficient accumulation of the drug and dose‐dependent cytotoxicity. Our system demonstrated to be redox‐activated, with efficiency comparable to the free drug in vitro. Grant Funding Source : Supported by NIH Research Initiative for Scientific Enhancement (RISE) Program with grant number: 2R25GM061151‐12.
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Key words
photodynamic therapy,nanoparticle,serum,albumin‐based
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