Radiomic signatures of pancreatic cancer can be extracted from CT scans, and this presents a unique and sensitive way to recover diagnostic information from treatments such as photodynamic therapy. While PDT of pancreatic cancer with Verteporfin induces large necrotic treatment zones, there is also a much more subtle alteration due to photodynamic priming (PDP). This effect alters collagen structures and changes the subsequent molecular signalling and sensitivity to adjuvant therapies. The approach to discovery of the key radiomic features will be discussed from both pre-clinical and clinical data sets, and the summary of the current clinical results will be presented.

The World Health Organization recently reported that more than 60% of new cancer cases and 70% of deaths annually occur in low and middle income countries (LMICs). This disparity motivates the development of low-cost cancer treatment and imaging technologies that are specifically adapted for use in LMIC settings. We have developed and clinically validated technology to enable use of photodynamic therapy (PDT) for treatment of early-stage oral malignancy in India, which has been described as the “oral cancer capital of the world.” Here we discuss challenges and opportunities moving forward for broader implementation of this technology in India and beyond.

Indoor-daylight photodynamic therapy (PDT) for actinic keratoses (AKs) could overcome the treatment limitations associated with conventional lamp-based PDT and outdoor sunlight treatments. The objective of this study was to compare the AK lesion clearance efficacy of a conventional treatment (30 minute of 5-aminolevulinic acid [ALA] preincubation, followed by 10 minutes of red light) versus indoor daylight treatment (30 minute of ALA pre-incubation, followed by 2 hours of indoor sunlight). A prospective clinical trial was conducted with 43 patients. The results of the study indicate that indoor sunlight-based PDT provides equivalent AK treatment efficacy to a conventional lamp-based regimen while overcoming temperature limitations associated with winter season outdoor sunlight treatments.

Rationally designed bioconjugates of photosensitizers have been shown to enhance the photochemical effect of photodynamic therapy (PDT) via altering the sub-cellular localization of the photosensitizers or modulating the function of ATP-binding cassette (ABC) transporters. P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are the two key members that contribute to chemoresistance and PDT resistance in cancer. Here, we introduce a porphyrin-based phospholipid conjugation strategy to circumvent and inhibit the efflux function of ABC drug transporters. Our results show the porphyrin-phospholipid conjugate enhances the photosensitizer accumulation and modulates the enzymatic activity and protein integrity of ABCB1 and ABCG2.

Combination treatments are most effective when targeting different cancer survival and growth pathways. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. In this study, we developed a light-activatable nanocomplex that selectively and simultaneously deliver three clinically relevant therapeutic agents at a synergistic drug ratio to destroy ovarian cancer cells, while sparing normal tissues.

Delayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue, with the origin of the signal comes from within or near the mitochondria of the cells. Here we developed a wide field system capable of real-time imaging of oxygen. During photodynamic therapy and FLASH radiation therapy (RT), oxygen is rapidly consumed in the targeted tissues and oxygen depletion is commonly known to occur. In both cases, we have used the pO2 imaging system to map out localized changes during treatment. We showed that mapping of partial oxygen pressure was possible at video rates up to 10 fps. This work also revealed that intracellular oxygen depletion is consequent during FLASH, bringing further clarification on the technique’s mechanism.

In order to safely and effectively treat patients with methylene blue photodynamic therapy (MB-PDT) for sterilization of deep tissue abscesses, abscess optical properties must be determined. We demonstrate the ability of our compact optical probe along with a Monte Carlo-based lookup table to retrieve optical properties in tissue simulating phantoms containing Intralipid as a scatterer, and Methylene Blue (MB) and/or Mn(III) meso-Tetra (4-sulfonatophenyl) porphine (MnTPPS) as absorbers. Our results demonstrate the system’s ability to accurately recover optical properties in the presence of multiple absorbers. Future applications for this system will allow for patient specific treatment throughout ongoing clinical trials.

This Conference Presentation, “Eutectic gallium-indium alloy based liquid metal nanoparticles for photoacoustic imaging and photodynamic therapy,” was recorded at SPIE Photonics West 2022 held in San Francisco, California, United States.

The mechanisms of photobiomodulation, beyond the light interaction with cytochrome C oxidase has been the subject of increasing focus in the past few years, but have yet to be fully elucidated. Research into the non-mitochondrial mechanisms is warranted in order to more fully explain photobiomodulation mechanism in order to garner greater acceptance in the traditional medical non-photobiomodulation field. This is especially important since the currently accepted central mechanism of action, the absorption of wavelengths by cytochrome-C-oxidase and the subsequent release of ROS and production of ATP, is being increasingly questioned. A narrative literature review was conducted across photobiomodulation, photochemistry and photophysical scientific published literature to gather information to integrate potential novel mechanisms of photobiomodulation. This presentation will examine some of these potential mechanisms beyond cytochrome-C-oxidase, including opsins as potential photobiomodulation targets and the associated non-visual phototransduction pathways, the potential of photobiomodulation to produce a photophysical effect to induce mechanotransduction pathways, the potential of photons to interact with proteins in micro-oscillatory cellular effects, including interaction with the cytoskeleton and the role of internally produced light. An overarching hypothesis for an integrated mechanism of light pathways will be presented, with implications for treatment of chronic pain, and neurodegenerative disease, including Parkinson’s and Alzeimer’s diseases.

Oral mucositis (OM) is a common side effect of radiation therapy for cancers, which has major consequences for the patient including severe pain, systemic infections, reduced nutritional intake, and adverse quality of life. The standard care currently available for OM is symptomatic, mainly directed towards pain remission (topical analgesics and parenteral drugs) and the prevention of secondary infection which have effect in the prevention and management of OM. Photobiomodulation therapy (PBMt) has been shown to stimulate tissue regeneration, reduce inflammation and control pain. The National Institute for Health and Care Excellence (NICE) has included PBMt as recommended therapy for preventing OM caused by radiotherapy or chemotherapy, and the Multinational-Association of Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO) found the evidence for LLLT/PBMt in the prevention of OM in patients to be safe and potentially very effective. A Quality Assurance study of the efficacy of pre-emptive PBMt to prevent/reduce severity of OM in radiotherapy patients was conducted at the San Hospital in Australia. Patients were given PBMt daily from before radiotherapy and throughout therapy, including home-treatment when the clinic could not be attended. Results were clinically positive, with no patient in the study developing OM beyond level 1. One participant presented a unique opportunity to compare OM treatments and outcomes, as his twin brother suffered the same cancer and was treated with the same radiation therapy, but without PBMt, a number of years previously. Implications of the therapy will be discussed.

Surgically induced inflammation is well known to create immunosuppression, potentially altering the efficacy of subsequently delivered therapies. When photodynamic therapy (PDT) is delivered during the peak of an inflammatory response to surgery, we have found it to alter the ability of PDT to generate antitumor immunity. These immunosuppressive effects of surgery can be transferred by multiple mechanisms that include splenocyte-derived T cells as well as though the generation of myeloid derived suppressor cells. These data support the study of immunomodulatory approaches to combat the inflammatory aspects of surgery when it is combined with PDT, or potentially other therapies.

Chronic kidney disease (CKD) is a worldwide public health problem, resulting in a significant burden on the health system. PBM is effective in mitigating inflammation, mitochondrial dysfunction, and oxidative stress, all of which are factors inherent in CKD. The aim of this study was to identify the direct effects of PBM in an in-vitro model of CKD. In vitro human proximal tubular cells (HK2 cells) were pre-treated with low (1.38 J/cm²) or high dosage (2.75J/cm²) of PBM. Cells were then incubated with TGF-β1 (2 ng/ml) for 48 hours with or without PBM irradiation every 24 hours. The SHAM groups were processed under the exact same conditions except in the absence of PBM irradiation. The expression levels of inflammatory markers monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fibrotic marker fibronectin (FN), antioxidative markers superoxide dismutase 1 (SOD1) and SOD2 were measured by qRT-PCR or ELISA The results showed that TGF-β1 significantly increased MCP-1, TNF-α, and fibronectin mRNA expression in HK2 cells, which was significantly reversed by the low dosage of PBM (0.45 J/cm², P<0.05), but not the higher dosage of PBM (0,9 J/cm²) when compared with the SHAM control group. The dose-response characteristics of PBM observed in this study followed the biphasic pattern. In conclusion, the present study suggests that PBM directly reduced inflammation and fibrosis in kidney tubular cells when used at the appropriate dose.

Photonanomedicines (PNMs) are photochemically-activated nanoscale drug delivery systems that play a niche role in photodynamic therapy (PDT)-based anticancer modalities. PNMs serve as versatile platforms for multi-agent delivery, spatiotemporally-controlled treatment induction and customization for tumor targeting. This work focuses on the systematic tuning of PNMs to achieve precision in tumor targeted photomodulation at three different scales: 1) stroma and interstitium, 2) proto-oncogenic cellular receptors, and 3) subcellular organelles (Figure 1). We show that photomodulation of tumors targeted at these three scales provides unique avenues to circumvent problematic barriers in drug delivery, treatment specificity, safety and tolerability, and treatment response.

Biodetection of inflammatory and disease-related targets is achieved using a portable quantitative large-area binding (QLAB) sensor. This sensor utilizes lens-free holographic microscopy, computational image processing involving pixel super-resolution, a custom LED array and microfluidic chip, and automated feature quantification algorithm to detect microbead agglutination in the presence of a target molecule or pathogen in solution. Here, we discuss a recent application involving biodetection of interferon-gamma (IFN-gamma) in solution where the QLAB sensor achieved a sensitivity of < 3 ng/mL We also discuss current work using this technology to sense SARS-CoV-2 in a point-of-care setting.

Alzheimer’s disease is caused by neurodegeneration resulting in cognitive decline, that has been linked to heightened systemic inflammation. Identification of the characteristic amyloid-β (Aβ) plaques in the brain is either by positron-emission tomography (PET) imaging or through its measurement in cerebrospinal fluid (CSF). A minimally invasive, cost-effective test that measures blood-based biomarker could predict the onset of Alzheimer’s earlier and therefore start therapies to improve patient prognosis. To this end, we have developed lateral-flow tests that measure vascular biomarkers, ICAM-1 and VCAM-1 and have validated their clinical use with serum samples.

Vaccines for the COVID-19 pandemic are limited and so effective drugs are needed. The binding affinity of several SARS-CoV-2 variants to human ACE2 receptors was measured using a frequency-locked optical whispering evanescent resonator (FLOWER) system. The advantage of FLOWER is that it is label-free and so drug candidates do not need to be labeled and it is ultra-sensitive so drugs over a wide range of binding affinities can be tested. The dissociation equilibrium constants of spike-RBD wild type as well as two variants, were analyzed and compared. Several drug candidates which inhibit the spike-RBD binding to ACE2, predicted by in-silico simulation, were screened using a competitive binding assay and the corresponding inhibitor constants were measured.

Catalase plays an essential role in degrading hydrogen peroxide (H2O2), which is one of the major enzymatic ROS scavenging mechanisms. Here, using wild-type Candida albicans along with its catalase-deficient mutant, we report that catalase inside fungi could be effectively and universally inactivated by blue light 410 nm, subsequently rendering these pathogens extremely sensitive to H2O2 and ROS-generating agents. This strategy could also significantly eradicate multiple notorious clinical Candida strains, including Candida auris. The antimicrobial efficacy of catalase photoinactivation is further validated using immune cell co-culturing system and a Candida albicans-induced mouse model of skin abrasion. Taken together, our findings offer a novel catalase-targeting approach against multidrug-resistant fungal infections.