Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer

Abstract

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.

CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer

“…In addition to NIR-PIT, other strategies to develop targeted photosensitizer for urologic cancer are under development. For example, Lin and colleagues described a multifunctional nanoporphyrin platform using a bladder cancer-targeting peptide PLZ4 (32). They report promising results with the PLZ4nanoporphyrin (PNP) in a patient-derived xenograft model of bladder cancer, showing PNP function integrating PDD, PDT, photothermal therapy (PTT), and targeted chemotherapy.…”

A Step‐by‐Step Multiple Stimuli‐Responsive Nanoplatform for Enhancing Combined Chemo‐Photodynamic Therapy

“…PDT, an important noninvasive therapeutic modality, has been clinically approved for cancer treatment. [46][47][48] Furthermore, light irradiation is considered to be an ideal noninvasive stimulus that can precisely treat the tumor with facile, flexible, and spatiotemporal control. [5] It has been documented that PDT as an external stimuli can compensate for the reduced therapeutic efficacy of conventional chemotherapy.…”

Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study

“…4). These issues contribute to tumor recurrence after conventional tumor resection [30,31] because surgeons can solely depend upon their eyes to visualize tumor tissue. We demonstrated a significant reduction in the recurrence rate and an increase in survival in mice simply by examining the surgical wound for residual disease and using probe-based NIR imaging-guided resection prior to wound closure.…”