Triple-negative breast cancer (TNBC) is a subtype of the breast cancer that represents around 20% of all invasive breast cancer, which main characteristics is resistance to conventional treatments, such as exposure to ionizing radiation (IR). On the order hand, photodynamic therapy (PDT) using porphyrins has been described in the literature as a potential therapy against cancer and currently with the advance of nanomedicine, nanoparticles (NPs) have been used to deliver the photosensitizer with greater precision mainly in deep tumor. Thus, our goal in this work was to develop a NP coated with TMPyP and associate it with IR in the treatment of TNBC.

Cherenkov imaging provides a valuable tool for the quality assurance of dose homogeneity in total skin electron therapy (TSET), in which patients were treated in six different postures using the Stanford standing technique. The emitted Cherenkov signals can be captured by three Cherenkov cameras, converted to 2D dose maps after certain corrections, and projected onto the patient specific 3D model to evaluate the cumulative total skin dose distribution. This study aims to improve the accuracy and reliability of Cherenkov converted dose obtained from the combination of multi-view Cherenkov images. The extra correction factors are investigated by conducting manikin phantom experiments as well as GAMOS based Monte Carlo simulations, and validated with in vivo dosimetry (IVD). We have also calibrated the side cameras and achieved a straightforward conversion of all Cherenkov images into doses using only the front camera. We have improved the Cherenkov-to-dose correction and conversion method, significantly reducing the deviation between the Cherenkov-converted dose and IVD measurements.

Pancreatic cancer is the fourth leading cause of cancer deaths. The poor diagnosis, early metastasis, limited drug accumulation in the tumor microenvironment, and acquired resistance to salvage chemotherapeutic cocktails lead to poor clinical outcomes. To overcome this complex problem, personalized combination treatments have been proposed to guide the clinical management of PDAC patients. In this context, we propose the use of novel delivery systems where light is not a mere spectator, but the main character that apart from inducing cytotoxicity also promotes the release of the cargo at the right time in the right place.

The efficacy of ALA PDT in targeting tumour cells depends on the extent of PpIX accumulation at the target site. Targeting PpIX bioconversion enzyme FeCH and efflux transporter ABCG2 helps overcome intrinsic resistance to the therapy. However, the factors contributing to the development of acquired resistance to PDT are lesser known. Here we show that repeated exposure to ALA PDT results in the downregulation of PpIX biosynthetic machinery to a greater extent compared to the PpIX bioconversion by FeCH or its efflux by ABCG2. Overall, this study highlights the mechanisms involved in the development of acquired resistance to ALA PDT in tumour cell lines.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) holds great promise as a treatment option for human basal cell carcinoma (BCC), the most common of all cancers. Recent evidence suggests that PDT is an immune-altering modality. Here we describe a clinical trial (NCT05020912) to examine the effects of ALA-PDT upon the tumor immune landscape within BCC tumors pre- and post-treatment, to better understand the nature of the tumor-infiltrating immune cells, and accompanying changes in systemic anti-tumor immunity. If better understood, such knowledge could be harnessed to improve therapeutic responses to PDT.

Protoporphyrin IX (PPIX) is an endogenous photosensitizer synthesized inside mitochondria by administering 5-aminolevulinic acid (ALA). With that in mind, it is important to understand the effects and mechanisms of PDT with PPIX directly on mitochondria at the bioenergetic level. This study evaluated mitochondrial respiration and swelling after in vitro PDT treatment at 635 nm in isolated mice liver mitochondria. Overall, respiration after PDT treatment showed an increase in mitochondria proton leak, reducing the respiratory control ratio (RCR) and coupling efficiency, and promoting a partial loss of cytochrome c, proportionally higher as the PPIX concentration or light dose increased. Besides, it also promoted mitochondrial swelling due to the opening of the mitochondrial permeability transition pore. These results indicate that PDT using PPIX as a photosensitizer probably causes damage to mitochondrial membranes, impairing respiration, which can contribute to cell death afterward.

Dissolving microneedles (DMNs) is a non-invasive intradermal or systemic drug delivery system. Considering topical photodynamic therapy (PDT) for non-melanoma skin cancer treatment, limited cream permeation is one of the main issues. In this context, DMNs can improve the prodrugs permeation providing photosensitizer distribution within lesions. This study explored DMNs containing aminolevulinic acid (ALA) with Gantrez AN-139 considering manufacturing protocols, mechanical resistance, insertion capability, ALA distribution homogeneity, and performance in a human xenographic tumor model induced in balb/c mice.

Photodynamic therapy (PDT) is a minimally invasive therapy that uses a photosensitizer in combination with light and oxygen to stimulate cell death. ALA-PDT has been approved as an intraoperative imaging agent in patients with high grade glioma. This research investigates the inhibition of PpIX efflux by lapatinib, in combination with the inhibition of PpIX bioconversion by deferoxamine to further increase intracellular PpIX in glioma cell lines. It can be concluded that intracellular PpIX accumulation can be achieved by inhibiting both PpIX efflux and bioconversion leading to cell death in a cell line dependent manner.

Oxygen's pivotal role in biology extends to oncology, affecting photodynamic therapy, radiotherapy, and chemotherapy efficacy. While invasive oxygen electrodes are the standard for in vivo measurement, they lack cellular information and are limited to single point measurements. Alternatively, noninvasive optical oxygen probes, quenching in the presence of oxygen, offer fast spatially resolved insights. However, limited FDA approval restricts their clinical use. In this study, we explore the use of the endogenous molecule protoporphyrin IX (PpIX), to measure tissue oxygen, using a novel fluorescence imaging approach. Our goal is to calibrate the PpIX ratiometric signal for precise pO2 measurements. We demonstrate the correlation between PpIX ratiometric signal and tissue oxygen and present an estimated correlation curve. This advancement in non-invasive intracellular measurement holds profound implications across medical disciplines, and particularly for PDT.

Here, a holographic sensor technology capable of measuring the dose received at the patient treatment site during daylight photodynamic therapy (D-PDT) is presented. The proposed transmission-mode holographic sensor enables more precise, customized dosimetry, with the objective of quantifying the weighted PPIX dose a patient receives, facilitating the potential for further optimization of therapies. The experimental development and optimization of the photosensitive film-based holographic sensor for D-PDT dosimetry is described. Both the photosensitive film fabrication process and the two-beam interferometric recording of holographic gratings have been optimized. Preliminary findings support the suitability of holographic gratings for D-PDT dosimetry.

Head and neck cancer (HNC) presents challenges due to its heterogeneity, high recurrence rate, and hypoxic microenvironments. Current treatments fall short, leading to high morbidity and mortality. Photodynamic therapy (PDT) offers spatiotemporal tumor control but relies on oxygenation, posing limitations in hypoxic tumors. Combining hypoxia-activated prodrugs with PDT can selectively kill hypoxic tumor cells and reduce the tumor burden. This study proposes using evofosfamide, a hypoxia-activated prodrug, in combination with benzoporphyrin derivative (BPD)-PDT in a 3D spheroids model of HNC. The growth profile, BPD uptake profile, and hypoxia development were investigated. Combination therapy enhanced PDT efficacy in hypoxic HNC spheroids.

Within 24 hours post treatment, photodynamic therapy causes a drastic reduction in tumor oxygenation and an increase in ultrasound scattering. While these trends can lead to determining acute tumor response, monitoring vascular and structural dynamics through 72 hours post treatment using ultrasound guided photoacoustic imaging provides a better insight on long-term PDT outcomes.

Peritoneal metastasis, incomplete resection, and drug resistance render advanced-stage ovarian cancer virtually incurable with current surgical and chemotherapy approaches. Photoimmunotherapy is increasingly used to treat unresectable metastases, but many innovations are lost in translation due to heterogeneous treatment effects. This study integrates targeted nanotechnology, fluorescence-guided intervention, and a medical laser system to improve the safety, efficacy, and consistency of photoimmunotherapy for peritoneal metastases.

As photodynamic therapy is reliant on endogenous tumor oxygen to be successful, personalizing treatment to the patient is a necessary step to improving overall efficacy. We have demonstrated the feasibility of functionally imaging PDT in real-time, by mapping oxygen saturation as a surrogate marker for PDT progression with ultrasound-guided photoacoustic imaging in vivo. Particularly, we have deciphered the spatial map of the oxygen depletion rate during PDT as a function of fluence rate. Photoacoustic imaging importantly provides the temporal and spatial resolution, providing a novel platform for monitoring that can be used to inform personalized treatment in future work.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide, with 800,000 deaths per year. Since surgical options for HCC patients are limited, minimally invasive ablative therapies are critical to treat early-stage HCC; however, their cost and need for specialized equipment and expertise prevent widespread use in underprivileged populations. Here, we propose a lower-cost Light-Activatable, Sustained-exposure Ethanol Injection Technology (LASEIT) to augment current options for underprivileged patients.

Countless trials of chemotherapy and/or targeted agent combinations have failed to produce substantial gains in survival for patients with pancreatic ductal adenocarcinoma. Recent studies have demonstrated exciting potential of RNA medicine approaches to therapeutically target microRNAs (miRNA, small non-coding RNAs) either by inhibiting tumor promoting miRNAs (onco-miRs) or enriching tumor suppressor miRNAs. Here we use co-culture and murine models to show that photodynamic therapy (PDT) using verteporfin both improves delivery and synergizes mechanistically with tumor suppressive effects of miR-146a-5p. These results indicate promise RNA medicine strategies for PDAC and could have broader applicability in therapeutic delivery of RNA medicine to solid tumors.

5-fluorouracil (5FU) and photodynamic therapy (PDT) are two popular cancer therapies that induce long-term anti-tumor immunity, mediated by cells of the innate and adaptive immune systems, in addition to their primary tumor-killing effects. The 5FU pretreatment combination with PDT (cPDT), involving the application of aminolevulinic acid (ALA), accumulation of protoporphyrin IX (PpIX) in tumors, and exposure to blue light results in lesion clearance mainly by immunological cell death. When combined, 5FU and PDT potentiate the generation of anti-tumor immune responses, resulting in a greater tumor reduction than is possible with either treatment modality given alone.