Mucosal Penetrating Bioconjugate Coated Upconverting Nanoparticles That Integrate Biological Tracking and Photodynamic Therapy for Gastrointestinal Cancer Treatment.

The integration of noninvasive photodynamic therapy (PDT) and imaging in the gastrointestinal tract is extremely challenging because of the limited light penetration in traditional PDT, and physiological barriers such as inorganic salts and mucous layers. Herein, d-α-tocopherol polyethylene glycol 1000 succinate-succinic acid-mercapto-ethylamine (TPGS-SH) was used to functionalize upconverting nanoparticles (UCNPs) and endow the modified UCNPs@TPGS-SH nanoparticles with excellent hydrophilic properties, biocompatibility, gastrointestinal stability and mucus penetration. After loading the photosensitizer zinc phthalocyanine (ZnPC) onto UCNPs@TPGS-SH, the resulting nanosystem ZnPC-UCNPs@TPGS-SH converted near-infrared light (NIR) to visible light, which activated ZnPC to generate singlet oxygen that showed a strong killing effect in Caco-2 cells. In-situ mucosal penetration assay showed that ZnPC-UCNPs@TPGS-SH accumulated more in the enterocytes of duodenum, jejunum and ileum, and less in the mucosal layer compared to ZnPC-UCNPs@TPGS. Moreover, cellular uptake and in situ tracing experiments confirmed that the florescent light emitted by UCNPs upon upconversion of deep penetrating NIR light could also serve as an imaging probe. These findings demonstrate the promising potential of this theranostic nanosystem for simultaneous deep penetrating biological tracing and PDT in gastrointestinal cancer.