Enhancing the Efficacy of Radiation Therapy by Photochemical Internalization of Fibrin-Hydrogel-Delivered Bleomycin.

Background/objectives: Although the use of radiation-sensitizing agents has been shown to enhance the effect of radiation on tumor cells, the blood-brain barrier (BBB) impedes these agents from reaching brain tumor sites when provided systemically. Localized methods of sensitizer delivery, utilizing hydrogels, have the potential to bypass the blood-brain barrier. This study examined the ability of photochemical internalization (PCI) of hydrogel-released bleomycin to enhance the growth-inhibiting effects of radiation on multi-cell glioma spheroids in vitro.

Corrigendum: Light-enhanced VEGF/rGel induce immunogenic cell death and increase the antitumor activity of αCTLA4 treatment.

[This corrects the article DOI: 10.3389/fimmu.2023.

Light-enhanced VEGF/rGel induce immunogenic cell death and increase the antitumor activity of αCTLA4 treatment.

Background: Immune-checkpoint inhibitors (ICIs) represent a revolution in cancer therapy and are currently implemented as standard therapy within several cancer indications. Nevertheless, the treatment is only effective in a subset of patients, and immune-related adverse effects complicate the improved survival. Adjuvant treatments that can improve the efficacy of ICIs are highly warranted, not only to increase the response rate, but also to reduce the therapeutic ICI dosage.

Phonetic characteristics of German unstressed vowels: The case of opa vs Oper.

Kohler [Einführung in die Phonetik des Deutschen (Erich Schmidt Verlag, Berlin, Germany, 1995)] stated that German [ɐ] and [a] in unstressed syllables are merging. The present study tested this hypothesis. The contrast was found intact word-internally and word-finally.

Small anticancer drug release by light: Photochemical internalization of porphyrin-β-cyclodextrin nanoparticles.

Aiming to engineer simple, neutral, strongly amphiphilic photoactive nanoparticles (NPs) to specifically target cancer cell lysosomes for drug transport and light-controlled release, new conjugates of β-cyclodextrin with highly hydrophobic triphenylporphyrin bearing different alkyl chains, were synthesized. Although differently sized, all conjugates self-assemble into ~60 nm NPs in water and display similar photoactivity. The NPs target selectively the lysosomes of breast adenocarcinoma MCF-7 cells, embedding in vesicular membranes, as experiments with model liposomes indicate.

Inhibition of glioma development by doxorubicin-photochemical internalization generated macrophage vaccine: A survival study in rats.

Background: The process known as immunogenic cell death (ICD) is characterized by dead and dying cancer cells exposing and releasing so-called damage associated molecular patterns (DAMPs). ICD has been shown to enhance the efficacy of antigen presenting cell (APC) immunotherapy. Both anthracycline drugs such as doxorubicin (DOX), and photodynamic therapy (PDT) have been shown to be inducers of ICD.

RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.

HER2 is a predictive biomarker for HER2-targeted therapeutics. For antibody-drug conjugates (ADCs; e.g.

Squamous cell carcinoma of the ear treated by photochemical internalization.

A 77-year-old Caucasian male was diagnosed with squamous cell cancer of the right ear. The patient elected to take part in the first-in-man phase I TPCS based bleomycin photochemical internalization (PCI). On Day 0, The patient received the photosensitiser [Amphinex (TPCS)], by slow intravenous injection.

Reactive Species from Two-Signal Activated Macrophages Interfere with Their Oxygen Consumption Measurements.

Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, we have reported a key role of nitric oxide (NO) in two(2)-signal activated macrophages [M(2-signals)].

An improved in vitro photochemical internalization protocol for 3D spheroid cultures.

Photochemical internalization (PCI) is a modified form of photodynamic therapy (PDT) that enhances the efficacy of therapeutic agents in a site and temporal specific manner in both in vitro and in vivo publications. The purpose of the study reported here was to evaluate the benefits of a modified PCI protocol in a 3D rat glioma spheroid model. In the modified protocol, F98 glioma cells were incubated with photosensitizer (AlPcS) prior to spheroid generation, as opposed to post-spheroid formation photosensitizer exposure commonly used in conventional protocols.

Enhanced gene transfection of macrophages by photochemical internalization: Potential for gene-directed enzyme prodrug therapy of gliomas.

Background: Drawn by tumor synthesis of chemo-attractive factors, macrophages are frequently found in and around glioblastomas and play an important role both in augmenting as well as inhibiting tumor growth. Patient-derived macrophages have the potential, therefore, to act as targeted delivery vectors for a variety of anti-cancer treatments. Among these is ex vivo gene transfection and re-injection back into the patient of macrophages to target residual tumors.

Word class and spelling in English.

The spelling of an English word may reflect its part of speech, not just the sounds within it. In 2 preregistered experiments, we asked whether university students are sensitive to 1 effect of part of speech that has been observed by linguists: that content words (e.g.

Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier.

Fibrin glue (FG) has potential as a delivery vehicle for photosensitizer directly to the resection cavity, so it may bypass the blood-brain barrier (BBB) and increase the concentration of successfully delivered photosensitizer. A specialized form of photodynamic therapy (PDT), photochemical internalization (PCI), which involves both photosensitizer and chemotherapeutic agent internalization, can locally inhibit the growth of cells. This will allow the reduction of recurrence of malignant gliomas around surgical resection.

Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic "Stealth" Nanoparticles for Cancer Therapy.

Hybrid porous nanoscale metal organic frameworks (nanoMOFs) made of iron trimesate are attracting increasing interest as drug carriers, due to their high drug loading capacity, biodegradability, and biocompatibility. NanoMOF surface modification to prevent clearance by the innate immune system remains still challenging in reason of their high porosity and biodegradable character. Herein, FDA-approved lipids and poly(ethylene glycol) (PEG)-lipid conjugates were used to engineer the surface of nanoMOFs by a rapid and convenient solvent-exchange deposition method.

Predictive biomarkers for 5-ALA-PDT can lead to personalized treatments and overcome tumor-specific resistances.

Background: Photodynamic therapy (PDT) is a minimally invasive, clinically approved therapy with numerous advantages over other mainstream cancer therapies. 5-aminolevulinic acid (5-ALA)-PDT is of particular interest, as it uses the photosensitiser PpIX, naturally produced in the heme pathway, following 5-ALA administration. Even though 5-ALA-PDT shows high specificity to cancers, differences in treatment outcomes call for predictive biomarkers to better stratify patients and to also diversify 5-ALA-PDT based on each cancer's phenotypic and genotypic individualities.

Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model.

Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR-overexpressing human head/neck OSC-19-luc2-cGFP tumor with transfected GFP gene was used in a skin-fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses.

Photodynamic Efficacy of Cercosporin in 3D Tumor Cell Cultures.

In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines.

Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research.

Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin.

In-Vivo Optical Monitoring of the Efficacy of Epidermal Growth Factor Receptor Targeted Photodynamic Therapy: The Effect of Fluence Rate.

Targeted photodynamic therapy (PDT) has the potential to improve the therapeutic effect of PDT due to significantly better tumor responses and less normal tissue damage. Here we investigated if the efficacy of epidermal growth factor receptor (EGFR) targeted PDT using cetuximab-IRDye700DX is fluence rate dependent. Cell survival after treatment with different fluence rates was investigated in three cell lines.

Apparent Complete Response of a Treatment Refractory and Recurrent Squamous Cell Carcinoma Lesion to Photochemical Internalization: A Clinical Case Study.

Photochemical internalization (PCI) depends on the delivery of sublethal photodynamic reaction to facilitate the work of a chemotherapeutic agent. We discuss our experience in managing a patient with extensive squamous cell carcinoma of the right face and scalp under the TPCS -based bleomycin PCI treatment protocol. In this case, an 84-year-old Caucasian received 0.

Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization.

The objective of this study was to develop and explore a novel CD133-targeting immunotoxin (IT) for use in combination with the endosomal escape method photochemical internalization (PCI). scFvCD133/rGelonin was recombinantly constructed by fusing a gene (scFvCD133) encoding the scFv that targets both non-glycosylated and glycosylated forms of both human and murine CD133/prominin-1 to a gene encoding the ribosome-inactivating protein (RIP) gelonin (rGelonin). RIP-activity was assessed in a cell-free translation assay.

The effects of low irradiance long duration photochemical internalization on glioma spheroids.

Background: Photodynamic therapy (PDT), if given over extended time periods (i.e. hours or days) and at very low irradiance in the μW/cm range, has been shown to be more effective than acute PDT (aPDT) administered over minutes.