Size‐dependent Tumor Response to Photodynamic Therapy and Irinotecan Monotherapies Revealed by Longitudinal Ultrasound Monitoring in an Orthotopic Pancreatic Cancer Model

Self Cite

Photodynamic therapy (PDT) is a phototoxic treatment with high spatial and temporal control and has shown tremendous promise in the management of cancer due to its high efficacy and minimal side effects. PDT efficacy is dictated by a complex relationship between dosimetry parameters such as the concentration of the photosensitizer at the tumor site, its spatial localization (intracellular or extracellular), light dose and distribution, oxygen distribution and concentration, and the heterogeneity of the inter‐ and intratumoral microenvironment. Studying and characterizing these parameters, along with monitoring tumor heterogeneity pre‐ and post‐PDT, provides essential data for predicting therapeutic response and the design of subsequent therapies. In this review, we elucidate the role of ultrasound (US) and photoacoustic imaging in improving PDT‐mediated outcomes in cancer—from tracking photosensitizer uptake and vascular destruction, to measuring oxygenation dynamics and the overall evaluation of tumor responses. We also present recent advances in multifunctional theranostic nanomaterials that can improve either US or photoacoustic imaging contrast, as well as deliver photosensitizers specifically to tumors. Given the wide availability, low‐cost, portability and nonionizing nature of US and photoacoustic imaging, together with their capabilities of providing multiparametric morphological and functional information, these technologies are thusly inimitable when deployed in conjunction with PDT.

Section: Role Of Us Imaging In Pdtmentioning

confidence: 74%

Role of Ultrasound and Photoacoustic Imaging in Photodynamic Therapy for Cancer

Hester

Kuriakose

Nguyen

et al. 2020

Self Cite

“…Nal‐BPD and Nal‐PpIX were reproducibly synthesized via the freeze‐thaw extrusion method . A lipid composition of dipalmitoylphosphatidylcholine (DPPC), cholesterol and distearoylphosphatidylethanolamine‐methoxy polyethylene glycol (DSPE‐PEG) at a 20:10:1 molar ratio was used based on the clinically approved PEGylated nanoliposomal formulations .…”

Section: Resultsmentioning

confidence: 99%

“…Nanoliposomes containing BPD or PpIX within the bilayer (Nal‐BPD or Nal‐PpIX) were synthesized via freeze‐thaw extrusion as described previously . Briefly, dipalmitoylphosphatidylcholine (DPPC), cholesterol, distearoylphosphatidylethanolamine‐methoxy polyethylene glycol (DSPE‐PEG) and 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) (Avanti Polar Lipids, Alabaster, AL, USA) were codissolved with BPD (50 nmoles, U.S. Pharmacopeia, Rockville, MD, USA) at 0.15 mol% BPD‐to‐lipid ratio or PpIX (60 nmoles, Santa Cruz Biotechnology, Dallas, TX, USA) at 0.18 mol% PpIX‐to‐lipid ratio.…”

Section: Methodsmentioning

confidence: 99%

Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain

Inglut

Gaitan

Najafali

et al. 2019

Fluorescence‐guided surgery (FGS) is routinely utilized in clinical centers around the world, whereas the combination of FGS and photodynamic therapy (PDT) has yet to reach clinical implementation and remains an active area of translational investigations. Two significant challenges to the clinical translation of PDT for brain cancer are as follows: (1) Limited light penetration depth in brain tissues and (2) Poor selectivity and delivery of the appropriate photosensitizers. To address these shortcomings, we developed nanoliposomal protoporphyrin IX (Nal‐PpIX) and nanoliposomal benzoporphyrin derivative (Nal‐BPD) and then evaluated their photodynamic effects as a function of depth in tissue and light fluence using rat brains. Although red light penetration depth (defined as the depth at which the incident optical energy drops to 1/e, ~37%) is typically a few millimeters in tissues, we demonstrated that the remaining optical energy could induce PDT effects up to 2 cm within brain tissues. Photobleaching and singlet oxygen yield studies between Nal‐BPD and Nal‐PpIX suggest that deep‐tissue PDT (>1 cm) is more effective when using Nal‐BPD. These findings indicate that Nal‐BPD‐PDT is more likely to generate cytotoxic effects deep within the brain and allow for the treatment of brain invading tumor cells centimeters away from the main, resectable tumor mass.

“…There continues to be support for three major PDT research groups (University of Pennsylvania, Massachusetts General Hospital/Harvard and Roswell Park Cancer Center). There are implications for use of PDT in otherwise poorly‐responsive tumors, for example, pancreatic cancer and mesothelioma . At this point, an appreciation for what PDT can do appears to be limited to a few centers in the US.…”

Section: Discussionmentioning

confidence: 99%

Thomas J. Dougherty: An Appreciation

Kessel

2019

Without the efforts of Tom Dougherty, it is unlikely that photodynamic therapy would have been more than a minor biomedical curiosity. His contributions to the field not only involved demonstrating the clinical relevance of the procedure but organizing that eventually led to FDA approval. This report summarizes his contributions to the field and illustrates the scope of discoveries that became feasible after his work brought PDT to the attention of others and to assorted funding agencies.