Photodynamic Therapy for Bladder Cancers, A Focused Review^†

Area of Science:

• Oncology
• Biomedical Engineering
• Photochemistry

Background:

• Photodynamic therapy (PDT) was first approved for bladder cancer in 1993 but faced limitations due to side effects like bladder contraction.
• Non-muscle invasive bladder cancers are more amenable to PDT than muscle-invasive or metastatic types.
• Blue light cystoscopy utilizing protoporphyrin IX (PpIX) fluorescence was FDA-approved in 2010 for diagnosing non-muscle invasive bladder cancer.

Purpose of the Study:

• To review recent advancements in PDT for bladder cancer, focusing on novel photosensitizers and formulations.
• To explore strategies for minimizing PDT-induced side effects, including intravesical administration, targeted delivery, and light control.
• To investigate methods for enhancing the therapeutic efficacy and tumor selectivity of PpIX-based PDT, particularly through combination with prodrugs.

Main Methods:

• Summarizing recent research on photosensitizers and formulations for bladder cancer PDT.
• Analyzing strategies for intravesical administration, targeting, and light delivery to minimize side effects.
• Investigating the combination of PpIX-PDT with singlet oxygen-activatable prodrugs to enhance efficacy and tumor selectivity.

Main Results:

• New photosensitizers and formulations are being developed to improve PDT outcomes for bladder cancer.
• Combining PpIX-PDT with singlet oxygen-activatable prodrugs has shown potential to increase therapeutic efficacy and tumor selectivity.
• Preferential PpIX formation in cancer cells using prodrugs leads to reduced off-target toxicity.

Conclusions:

• Advancements in photosensitizers and formulations offer improved PDT strategies for bladder cancer.
• Combination therapies, such as PpIX-PDT with specific prodrugs, enhance treatment efficacy and safety.
• Future research should focus on optimizing prodrugs and light delivery for effective in vivo treatment with minimal bladder dysfunction.