Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids

Abstract

Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm2), and the dose rate (fluence rate in mW/cm2). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer.

Assays on 3D tumor spheroids for exploring the light dosimetry of photodynamic effects under different gaseous conditions

“…The underlying mechanism of PDT entails the activation of a photosensitizer (PS) by specific wavelengths of light, culminating in the generation of cytotoxic reactive oxygen species (ROS) that induce cellular apoptosis, vascular damage, or/and host immune response [2]. Key dosimetric variables that dictate the efficacy of PDT comprise the photophysical properties and selective uptake of the PS in targeted tissues, the availability of local oxygen, and the delivered light at the site of application [3,4]. Rapid preclinical screening with a compilation of a multitude of PDT parameters and pharmacological factors is favored prior to implementing optimal regimens in the clinic.…”