A photosensitizer-conjugated magnetic iron oxide/gold hybrid nanoparticle as an activatable platform for photodynamic cancer therapy†
Abstract
A multifunctional nanomedicine combining magnetic resonance imaging (MRI) and photodynamic therapy (PDT) functionalities is a promising integrated platform that allows for targeted drug delivery, noninvasive monitoring of therapeutic responses, and simultaneous cancer diagnosis and treatment. A hybrid nanoparticle (NP) system with a core/shell-structured magnetic iron oxide/gold (Fe3O4/Au) NP and a photosensitizer (PS)-conjugated heparin surface layer is investigated as a novel multifunctional carrier in PDT. A thiolated heparin–pheophorbide a (PhA) conjugate (H–PhA), which is a macromolecular PS, is synthesized and introduced onto the NP surface through a gold–thiol interaction. The photoactivity of the PhA moieties on the NP surface is significantly suppressed by the quenching effect of the Fe3O4/Au NP. However, their photoactivity can be restored in a glutathione (GSH)-rich intracellular environment, which allows GSH-mediated switchable photoactivity in the hybrid NP system. As a result, marked phototoxicity and strong fluorescence signals are observed in NP-treated A549 cells under light irradiation. In an animal tumor model, Fe3O4/Au/H–PhA NPs are efficacious in photodynamic cancer treatment and exhibit prolonged circulation characteristics, enhanced tumor specificity, and higher therapeutic efficacy compared with free PhA. In addition, in vitro MRI studies reveal that the NPs could potentially serve as MRI contrast agents in cancer diagnosis and may be used to monitor the photodynamic treatment response used to accurately guide light irradiation. The present findings show that the Fe3O4/Au/H–PhA NP is a promising nanomedicine platform in PDT and cancer diagnosis.
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