研究目的
Investigating the therapeutic effects of a glutathione- and light-controlled generation of singlet oxygen for triggering drug release in mesoporous silica nanoparticles.
研究成果
The study demonstrated a thiol-activatable ZnPc-based photosensitiser and a singlet-oxygen-triggered Dox releasing system incorporated into MSNs, forming a multifunctional nanoplatform. The photosensitising ability of the ZnPc units could be restored in an environment with elevated GSH concentrations, but remained inactivated in low GSH levels. The release of Dox in PBS could be achieved only with both pre-incubation with mM of GSH and the presence of light through the cleavage of the 9,10-dialkoxyanthracene linker by the singlet oxygen generated in situ. However, the cytotoxic effect of the released Dox could not be shown probably due to the reduced cytotoxicity as a result of the pendant substituent and the low drug loading in the MSNs.
研究不足
The cytotoxic effect of the released Dox moieties was not notable probably due to their reduced cytotoxicity as a result of the pendant substituent and the low drug loading in the nanoparticles. The study suggests that further modification of the nanosystems is necessary to achieve a synergistic therapeutic effect.
1：Experimental Design and Method Selection
The study involved the synthesis of a zinc(II) phthalocyanine (ZnPc) substituted with a glutathione-cleavable 2,4-dinitrobenzenesulfonate (DNBS) quencher and doxorubicin (Dox) linked via a singlet-oxygen-cleavable 9,10-dialkoxyanthracene linker. The ZnPc and Dox moieties were encapsulated into mesoporous silica nanoparticles (MSNs) to form a nanoplatform. The activation of ZnPc by glutathione (GSH) and the subsequent generation of singlet oxygen upon irradiation were studied to trigger the release of Dox.
2：Sample Selection and Data Sources
HepG2 human hepatocellular carcinoma cells were used to study the intracellular activation of ZnPc by thiols and the cytotoxicity of the nanosystem. Phosphate buffered saline (PBS) was used to study the GSH-responsive behavior and singlet-oxygen-triggered Dox release.
3：List of Experimental Equipment and Materials
Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to characterize the morphology and size of the nanoparticles. Spectrophotometers and spectrofluorometers were used for electronic absorption and fluorescence measurements. Confocal laser scanning microscopy and flow cytometry were used for in vitro studies.
4：Experimental Procedures and Operational Workflow
The synthesis of ZnPc and Dox derivatives, their encapsulation into MSNs, and the study of their GSH-responsive behavior and singlet-oxygen-triggered Dox release were performed. The cytotoxicity of the nanosystem was evaluated using the MTT assay.
5：Data Analysis Methods
The data were analyzed using software specific to the equipment used, such as TEM Imagine and Analysis Software, Malvern Zetasizer Software, Zeiss ZEN 2 software, and Leica Application Suite X software for microscopy and flow cytometry data.
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