The overall prognosis of
bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and
therapy approaches for
bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a
bladder cancer-specific
ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided
photodynamic therapy,
photothermal therapy and targeted
chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/
reactive oxygen species upon illumination with near infrared light.
Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in
bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived
bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis.
Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic
acid, and eliminated orthotopic PDX
bladder cancers after intravesical treatment. Image-guided photodynamic and
photothermal therapies synergized with targeted
chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted
tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against
bladder cancers. This platform can be easily adapted to
individualized medicine in a clinical setting and has tremendous potential to improve the management of
bladder cancer in the clinic.