Molecular fluorescence-guided surgery has shown promise for tumor margin delineation but is limited by its depth profiling capability. Interestingly, most fluorophores, either clinically approved or in clinical trials, can also be used as photoacoustic contrast agents, yet their use is limited due to the low light fluence permitted for clinical use and the limited sensitivity of current photoacoustic imaging systems. There is therefore an urgent unmet need to establish methods for enhancing contrast in molecular targeted PA imaging which could potentially complement and overcome limitations in molecular fluorescence guided therapies.
View Article and Find Full Text PDFSignificance: Fluorescence sensing within tissue is an effective tool for tissue characterization; however, the modality and geometry of the image acquisition can alter the observed signal.
Aim: We introduce a novel optical fiber-based system capable of measuring two fluorescent contrast agents through 2 cm of tissue with simple passive electronic switching between the excitation light, simultaneously acquiring fluorescence and excitation data. The goal was to quantify indocyanine green (ICG) and protoporphyrin IX (PpIX) within tissue, and the sampling method was compared with wide-field surface imaging to contrast the value of deep sensing versus surface imaging.
Superhydrophobic antimicrobial photodynamic therapy (SH-aPDT) is advantageous wherein airborne singlet oxygen (O) is delivered from a device tip to kill a biofilm with no photosensitizer exposure and no bacterial selectivity (Gram + or Gram -). For effective treatment of periodontitis, the frequency of treatment as well as the optical light fluence required is not known. Thus, we sought to determine whether single or repeated SH-aPDT treatments would work best in vivo using two fluence values: 60 and 125 J/cm.
View Article and Find Full Text PDFBackground: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.
Methods: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction.
The rise of antimicrobial resistance poses a critical public health threat worldwide. While antimicrobial photodynamic therapy (aPDT) has demonstrated efficacy against multidrug-resistant (MDR) bacteria, its effectiveness can be limited by several factors, including the delivery of the photosensitizer (PS) to the site of interest and the development of bacterial resistance to PS uptake. There is a need for alternative methods, one of which is superhydrophobic antimicrobial photodynamic therapy (SH-aPDT), which we report here.
View Article and Find Full Text PDFGlioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re-populate the tumor milieu due to selection following conventional therapies. Here, we show that 5-aminolevulinic acid (ALA) treatment-a pro-fluorophore used for fluorescence-guided cancer surgery-leads to elevated levels of fluorophore conversion in patient-derived GSC cultures, and subsequent red light-activation induces apoptosis in both intrinsically temozolomide chemotherapy-sensitive and -resistant GSC phenotypes. Red light irradiation of ALA-treated cultures also exhibits the ability to target mesenchymal GSCs (Mes-GSCs) with induced temozolomide resistance.
View Article and Find Full Text PDFTumor-targeted, activatable photoimmunotherapy (taPIT) has been shown to selectively destroy tumor in a metastatic mouse model. However, the photoimmunoconjugate (PIC) used for taPIT includes a small fraction of non-covalently associated (free) benzoporphyrin derivative (BPD), which leads to non-specific killing in vitro. Here, we report a new treatment protocol for patient-derived primary tumor cell cultures ultrasensitive to BPD photodynamic therapy (BPD-PDT).
View Article and Find Full Text PDFThe prognosis for patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) remains dismal. It is generally accepted that combination cancer therapies offer the most promise, such as Folforinox, despite their associated high toxicity. This study addresses the issue of chemoresistance by introducing a complementary dual priming approach to attenuate the DNA repair mechanism and to improve the efficacy of a type 1 topoisomerase (Top1) inhibitor.
View Article and Find Full Text PDFThe persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies.
View Article and Find Full Text PDFDesmoplasia in pancreatic ductal adenocarcinoma (PDAC) limits the penetration and efficacy of therapies. It has been previously shown that photodynamic priming (PDP) using EGFR targeted photoactivable multi-inhibitor liposomes remediates desmoplasia in PDAC and doubles overall survival. Here, bifunctional PD-L1 immune checkpoint targeted photoactivable liposomes (iTPALs) that mediate both PDP and PD-L1 blockade are presented.
View Article and Find Full Text PDFPhotodynamic therapy (PDT) is a nonscarring cancer treatment in which a pro-drug (5-aminolevulinic acid, ALA) is applied, converted into a photosensitizer (protoporphyrin IX, PpIX) which is then activated by visible light. ALA-PDT is now popular for treating nonmelanoma skin cancer (NMSC), but can be ineffective for larger skin tumors, mainly due to inadequate production of PpIX. Work over the past two decades has shown that differentiation-promoting agents, including methotrexate (MTX), 5-fluorouracil (5FU) and vitamin D (Vit D) can be combined with ALA-PDT as neoadjuvants to promote tumor-specific accumulation of PpIX, enhance tumor-selective cell death, and improve therapeutic outcome.
View Article and Find Full Text PDFImproved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects.
View Article and Find Full Text PDFSeveral molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) for head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual-function antibody conjugate (DFAC) for multimodal imaging and photoimmunotherapy (PIT) of EGFR-overexpressing cancer cells. The DFAC reported previously and used in the present study comprises an EGFR-targeted antibody, cetuximab, conjugated to benzoporphyrin derivative (BPD) for fluorescence imaging and PIT and a Si-centered naphthalocyanine dye for photoacoustic imaging.
View Article and Find Full Text PDFDesmoplasia in pancreatic ductal adenocarcinoma (PDAC) is characterized by elevated levels of tumor collagen. Desmoplasia restricts drug delivery in PDAC, contributes to treatment resistance, and is associated with poor survival outcomes. We have previously shown that photodynamic therapy (PDT)-based treatment remediates desmoplasia in orthotopic PDAC tumors by reducing second harmonic generation signals from collagen by >90% and by reducing collagen alignment by >10-fold [19].
View Article and Find Full Text PDFLimited options exist for treatment of periodontitis; scaling and root planing (SRP) are not sufficient to eradicate and the resulting inflammatory disease. Chlorhexidine (CHX), used as an adjuvant to SRP, may reduce bacterial loads but leads to pain and staining, while evidence for its efficacy is lacking. Antibiotics are effective but can lead to drug-resistance.
View Article and Find Full Text PDFPhotodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents.
View Article and Find Full Text PDFFluorescence-guided intervention can bolster standard therapies by detecting and treating microscopic tumors before lethal recurrence. Tremendous progress in photoimmunotherapy and nanotechnology has been made to treat metastasis. However, many are lost in translation due to heterogeneous treatment effects.
View Article and Find Full Text PDFOncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets.
View Article and Find Full Text PDFSignificance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed.
View Article and Find Full Text PDFVitamin D3, a prohormone, is converted to circulating calcidiol and then to calcitriol, the hormone that binds to the vitamin D receptor (VDR) (a nuclear transcription factor). Polymorphic genetic sequence variants of the VDR are associated with an increased risk of breast cancer and melanoma. However, the relationship between VDR allelic variants and the risk of squamous cell carcinoma and actinic keratosis remains unclear.
View Article and Find Full Text PDFSeveral molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) of head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual function antibody conjugate (DFAC) for multi-modal imaging and photoimmunotherapy (PIT) of EGFR over-expressing cancer cells. The DFAC reported previously and used in the present study, comprises of an EGFR targeted antibody - Cetuximab conjugated to Benzoporphyrin derivative (BPD) for fluorescence imaging and PIT, and a Si-centered naphthalocyanine dye for photoacoustic imaging.
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