Three-in-One Functional Silica Nanocarrier with Singlet Oxygen Generation, Storage/Release, and Self-Monitoring for Enhanced Fractional Photodynamic Therapy.

At present, the intermittent photodynamic therapy (fractional PDT) for overcoming tumor hypoxia still have their own defects, such as irradiation-dependence and rapid metabolism of organic photosensitizers. Therefore, it is still a really formidable challenge to achieve efficient fractional PDT. Herein, a three-in-one functional silica nanocarrier (FSNC) with singlet oxygen (1O2) generating unit (protoporphyrin IX derivative), 1O2 storage/release unit (2-pyridone derivative), and 1O2 self-monitoring unit (cyanine derivative) was prepared by reverse microemulsion method. Also, it could be efficiently internalized in the HeLa cells because of an appropriate particle size (∼44.8 nm). In the presence of light, the endoperoxide is formed to achieve 1O2 storage together with 1O2 generated by 1O2 generating unit for traditional PDT. In the absence of light, the endoperoxide produces 1O2 through cycloreversion for continuous PDT. As a result, the fractional PDT process of the FSNC on the HeLa cells performed a higher phototoxicity than traditional photosensitizer protoporphyrin IX. Furthermore, this real-time release behavior of 1O2 can be visually captured by confocal laser scanning microscope via monitoring fluorescent bleaching of 1O2 self-monitoring unit. Therefore, this fluorescent imaging-guided fractional PDT process could effectively enhance the PDT effect compared with traditional PDT.