Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor...

Area of Science:

• Oncology
• Biochemistry
• Nanomedicine

Background:

• Ovarian cancer (OC) frequently recurs in the peritoneum, necessitating novel therapeutic strategies.
• Targeting microscopic tumor residues is crucial for improving patient survival.
• Folates receptor alpha (FRα) is overexpressed on peritoneal OC metastasis, presenting a viable therapeutic target.

Purpose of the Study:

• To develop a targeted photodynamic therapy (PDT) for peritoneal carcinomatosis from OC.
• To create a vectorized photosensitizer (PS^FAA) targeting FRα using a novel folic acid analog (FAA).
• To evaluate the selectivity and efficacy of PS^FAA in OC models.

Main Methods:

• Synthesis of PS^FAA by conjugating pyropheophorbide-a (Pyro-a) to a novel FAA via a polyethylene glycol (PEG) spacer.
• Evaluation of PS^FAA selectivity and PDT efficacy on human OC cell lines overexpressing FRα and fibrosarcoma cells with low FRα expression.
• Assessment of photophysical properties, including fluorescence and singlet oxygen quantum yields.
• Analysis of PS^FAA toxicity and dose-dependent effects after light illumination.

Main Results:

• PS^FAA was synthesized with a 19% overall yield after 10 steps.
• PS^FAA exhibited photophysical properties similar to free Pyro-a, with fluorescence (Φ_f=0.26) and singlet oxygen quantum yields (Φ_Δ=0.41).
• No PS^FAA toxicity was observed; PDT efficacy was dose-dependent on PS concentration and light dose.
• PS^FAA-mediated PDT reduced pro-inflammatory cytokine (IL-6) secretion in OC cells.

Conclusions:

• The novel PS^FAA demonstrates promising selectivity and efficacy for targeted PDT of OC peritoneal metastasis.
• This targeted approach offers new therapeutic perspectives for ovarian cancer, addressing a significant unmet clinical need.
• The developed PS^FAA highlights the potential of vectorized photosensitizers in cancer therapy.