RESUMEN
Switchable phototheranostic nanomaterials are of particular interest for specific biosensing, high-quality imaging, and targeted therapy in the field of precision nanomedicine. Here, we develop a "one-for-all" nanomaterial that self-assembles from flexible and versatile phthalocyanine building blocks. The nanostructured phthalocyanine assemblies (NanoPcTBs) display intrinsically unique photothermal and photoacoustic properties. Fluorescence and reactive oxygen species generation can be triggered depending on a targeted, protein-induced, partial disassembly mechanism, which creates opportunities for low-background fluorescence imaging and activatable photodynamic therapy. In vitro evaluations indicate that NanoPcTB has a high selectivity for biotin receptor-positive cancer cells (e.g., A549) compared to biotin receptor-negative cells (e.g., WI38-VA13) and permits a combined photodynamic and photothermal therapeutic effect. Following systemic administration, the NanoPcTBs accumulate in A549 tumors of xenograft-bearing mice, and laser irradiation clearly induces the inhibition of tumor growth.
Asunto(s)
Indoles/química , Nanoestructuras , Fotoquimioterapia/métodos , Fotones , Fármacos Fotosensibilizantes/química , Animales , Línea Celular Tumoral , Fluorescencia , Xenoinjertos , Humanos , Indoles/uso terapéutico , Isoindoles , Ratones , Microscopía Electrónica de Transmisión , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Risk of teratoma formation during human pluripotent stem cell (hPSC)-based cell therapy is one of the technical hurdles that must be resolved before their wider clinical application. To this end, selective ablation of undifferentiated hPSCs has been achieved using small molecules whose application should be safe for differentiated cells derived from the hPSCs. OBJECTIVE: However, the functional safety of such small molecules in the cells differentiated from hPSCs has not yet been extensively validated. METHOD: We used the survivin inhibitor YM155, which induced highly selective cell death of hPSCs for ablating undifferentiated hESCs after differentiation to human mesenchymal stem cells (hMSCs) and examined whether hMSCs remained fully functional after being exposed by YM155. RESULTS: We demonstrated that human mesenchymal stem cells (hMSCs) derived from human embryonic stem cells (hESCs) remained fully functional in vitro and in vivo, while hESCs were selectively ablated. CONCLUSION: These results suggest that a single treatment with YM155 after differentiation of hMSCs would be a valid approach for teratoma-free cell therapy.