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Theranostics 2021Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis...
Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) into tumor tissues with high specificity. Exosome donor cells (HEK293T) were transfected with control or CD47-overexpressing plasmid. Exosomes were isolated and loaded with Er and RB via sonication method. Hepa1-6 cell xenograft C57BL/6 model was injected with control and engineered exosomes via tail vein. distribution of the injected exosomes was analyzed via tracking the fluorescence labeled exosomes. Photodynamic therapy was conducted by 532 nm laser irradiation. The therapeutic effects on hepatocellular carcinoma and toxic side-effects were systemically analyzed. CD47 was efficiently loaded on the exosomes from the donor cells when CD47 was forced expressed by transfection. CD47 surface functionalization (Exos) made the exosomes effectively escape the phagocytosis of mononuclear phagocyte system (MPS), and thus increased the distribution in tumor tissues. Erastin and RB could be effectively encapsulated into exosomes after sonication, and the drug-loaded exosomes (Er/RB@Exos) strongly induced ferroptosis both and in tumor cells after irradiation of 532 nm laser. Moreover, compared with the control exosomes (Er/RB@Exos), Er/RB@Exos displayed much lower toxicity in liver. : The engineered exosomes composed of CD47, Erastin, and Rose Bengal, induce obvious ferroptosis in hepatocellular carcinoma (HCC) with minimized toxicity in liver and kidney. The proposed exosomes would provide a promising strategy to treat types of malignant tumors.
Topics: Animals; CD47 Antigen; Carcinoma, Hepatocellular; Disease Models, Animal; Drug Delivery Systems; Exosomes; Ferroptosis; Fluorescent Dyes; HEK293 Cells; Heterografts; Humans; Kidney; Liver; Liver Neoplasms; Mice; Mice, Inbred C57BL; Photochemotherapy; Piperazines; Rose Bengal
PubMed: 34373736
DOI: 10.7150/thno.59121 -
Life (Basel, Switzerland) Sep 2022High-quality upconverting NaYF:Yb,Er nanoparticles (UCNPs; 26 nm in diameter) based on lanthanides were synthesized by a high-temperature coprecipitation method. The...
High-quality upconverting NaYF:Yb,Er nanoparticles (UCNPs; 26 nm in diameter) based on lanthanides were synthesized by a high-temperature coprecipitation method. The particles were modified by bisphosphonate-terminated poly(ethylene glycol) (PEG) and Rose Bengal (RB) photosensitizer. The particles were thoroughly characterized using transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, FTIR, and X-ray photoelectron and upconversion luminescence spectroscopy in terms of morphology, hydrodynamic size, composition, and energy transfer to the photosensitizer. Moreover, the singlet oxygen generation from RB-containing UCNPs was investigated using 9,10-diphenylanthracene probe under 980 nm excitation. The cytotoxicity of UCNPs before and after conjugation with RB was evaluated on highly sensitive rat mesenchymal stem cells (rMSCs) and significant differences were found. Correspondingly, consi-derable variations in viability were revealed between the irradiated and non-irradiated rat glioma cell line (C6) exposed to RB-conjugated UCNPs. While the viability of rMSCs was not affected by the presence of UCNPs themselves, the cancer C6 cells were killed after the irradiation at 980 nm due to the reactive oxygen species (ROS) production, thus suggesting the potential of RB-conjugated PEG-modified UCNPs for applications in photodynamic therapy of cancer.
PubMed: 36143419
DOI: 10.3390/life12091383 -
Translational Vision Science &... Jan 2022To examine and compare the efficacy of in vitro growth inhibition using rose bengal and riboflavin photodynamic antimicrobial therapy (PDAT) for Nocardia keratitis...
PURPOSE
To examine and compare the efficacy of in vitro growth inhibition using rose bengal and riboflavin photodynamic antimicrobial therapy (PDAT) for Nocardia keratitis isolates.
METHODS
Nocardia asteroides complex, Nocardia amikacinitolerans, and Nocardia farcinica species were isolated from patients with confirmed Nocardia keratitis. Isolates were tested against three experimental groups: (1) no photosensitizer/no irradiation, (2) photosensitizer/no irradiation, and (3) photosensitizer/irradiation. Each isolate was prepared in suspension to a concentration of 1.5 × 108 CFU/mL. Bacterial suspensions were mixed with water or prepared 0.1% photosensitizer solution for a final bacterial concentration of 1.5 × 107 CFU/mL. Aliquots of 1 mL were plated on 5% sheep blood agar. Rose bengal and riboflavin PDAT plates were irradiated for 15 minutes with a 525- or 375-nm custom 6-mW/cm2 powered light source for a total fluence of 5.4 J/cm2. All experimental groups were repeated in triplicate. Plates were incubated in a 35°C non-CO2 incubator for 96 hours and photographed. Percent inhibition was evaluated using LabVIEW-based software.
RESULTS
All strains of Nocardia tested with 0.1% rose bengal and irradiated for 15 minutes demonstrated statistically significant inhibition of growth (P < 0.05). No other experimental groups displayed any bacterial inhibition.
CONCLUSIONS
Rose bengal is superior to riboflavin PDAT against selected Nocardia isolates. In vivo testing is warranted to investigate the utility of rose bengal PDAT for severe Nocardia keratitis.
TRANSLATIONAL RELEVANCE
In vitro results for three clinical strains of Nocardia support the possible use of rose bengal PDAT as a complementary treatment of Nocardia keratitis.
Topics: Animals; Anti-Infective Agents; Florida; Humans; Keratitis; Nocardia; Riboflavin; Rose Bengal; Sheep
PubMed: 35044443
DOI: 10.1167/tvst.11.1.29 -
Pharmaceuticals (Basel, Switzerland) Aug 2022Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of... (Review)
Review
Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT.
PubMed: 36145315
DOI: 10.3390/ph15091093 -
ACS Omega Oct 2017We investigated two critical aspects of rose Bengal (RB) photosensitized protein cross-linking that may underlie recently developed medical applications. Our studies...
We investigated two critical aspects of rose Bengal (RB) photosensitized protein cross-linking that may underlie recently developed medical applications. Our studies focused on the binding of RB to collagen by physical interaction and the effect of this binding and certain amino acids on RB photochemistry. Molecular dynamics simulations and free-energy calculation techniques, complemented with isothermal titration calorimetry, provided insight into the binding between RB and a collagen-like peptide (CLP) at the atomic level. Electrostatic interactions dominated, which is consistent with the finding that RB bound equally well to triple helical and single chain collagen. The binding free energy ranged from -5.7 to -3 kcal/mol and was strongest near the positively charged amino groups at the N-terminus and on lysine side chains. At high RB concentration, a maximum of 16 ± 3 bound dye molecules per peptide was found, which is consistent with spectroscopic evidence for aggregated RB bound to collagen or the CLP. Within a tissue-mimetic collagen matrix, RB photobleached rapidly, probably due to electron transfer to certain protein amino acids, as was demonstrated in solutions of free RB and arginine. In the presence of arginine and low oxygen concentrations, a product absorbing at 510 nm formed, presumably due to dehalogenation after electron transfer to RB. In the collagen matrix without arginine, the dye generated singlet oxygen as well as the 510 nm product. These results provide the first evidence of the effects of a tissue-like environment on the photochemical mechanisms of rose Bengal.
PubMed: 31457260
DOI: 10.1021/acsomega.7b00675 -
International Journal of Molecular... Oct 2020For medical application, easily accessible biomaterials with tailored properties are desirable. Collagen type I represents a biomaterial of choice for regenerative...
For medical application, easily accessible biomaterials with tailored properties are desirable. Collagen type I represents a biomaterial of choice for regenerative medicine and tissue engineering. Here, we present a simple method to modify the properties of collagen and to generate collagen laminates. We selected three commercially available collagen sheets with different thicknesses and densities and examined the effect of rose bengal and green light collagen crosslinking (RGX) on properties such as microstructure, swelling degree, mechanical stability, cell compatibility and drug release. The highest impact of RGX was measured for Atelocollagen, for which the swelling degree was reduced from 630% (w/w) to 520% (w/w) and thickness measured under force application increased from 0.014 mm to 0.455 mm, indicating a significant increase in mechanical stability. Microstructural analysis revealed that the sponge-like structure was replaced by a fibrous structure. While the initial burst effect during vancomycin release was not influenced by crosslinking, RGX increased cell proliferation on sheets of Atelocollagen and on Collagen Solutions. We furthermore demonstrate that RGX can be used to covalently attach different sheets to create materials with combined properties, making the modification and combination of readily available sheets with RGX an attractive approach for clinical application.
Topics: Biocompatible Materials; Cell Proliferation; Cell Survival; Cells, Cultured; Collagen; Collagen Type I; Cross-Linking Reagents; Drug Liberation; Fluorescent Dyes; Humans; Molecular Structure; Muscle Cells; Osteoblasts; Rose Bengal; Tissue Donors; Tissue Engineering; Vancomycin
PubMed: 33049938
DOI: 10.3390/ijms21197408 -
Biomolecules Nov 2022Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a...
Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar O generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C alkyl (SARS-CoV-2) and C alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C congeners and a significant aggregation tendency for the C derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.
Topics: Humans; Rose Bengal; SARS-CoV-2; Photosensitizing Agents; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 36358961
DOI: 10.3390/biom12111609 -
Materials (Basel, Switzerland) Jan 2022Herein we report the development of a nanocomposite for X-ray-induced photodynamic therapy (X-PDT) and computed tomography (CT) based on PEG-capped GdF:Tb scintillating...
Herein we report the development of a nanocomposite for X-ray-induced photodynamic therapy (X-PDT) and computed tomography (CT) based on PEG-capped GdF:Tb scintillating nanoparticles conjugated with Rose Bengal photosensitizer via electrostatic interactions. Scintillating GdF:Tb nanoparticles were synthesized by a facile and cost-effective wet chemical precipitation method. All synthesized nanoparticles had an elongated "spindle-like" clustered morphology with an orthorhombic structure. The structure, particle size, and morphology were determined by transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) analysis. The presence of a polyethylene glycol (PEG) coating and Rose Bengal conjugates was proved by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and ultraviolet-visible (UV-vis) analysis. Upon X-ray irradiation of the colloidal PEG-capped GdF:Tb-Rose Bengal nanocomposite solution, an efficient fluorescent resonant energy transfer between scintillating nanoparticles and Rose Bengal was detected. The biodistribution of the synthesized nanoparticles in mice after intravenous administration was studied by in vivo CT imaging.
PubMed: 35057287
DOI: 10.3390/ma15020569 -
Scientific Reports Jul 2020The intracellular Tau aggregates are known to be associated with Alzheimer's disease. The inhibition of Tau aggregation is an important strategy for screening of...
The intracellular Tau aggregates are known to be associated with Alzheimer's disease. The inhibition of Tau aggregation is an important strategy for screening of therapeutic molecules in Alzheimer's disease. Several classes of dyes possess a unique property of photo-excitation, which is applied as a therapeutic measure against numerous neurological dysfunctions. Rose Bengal is a Xanthene dye, which has been widely used as a photosensitizer in photodynamic therapy. The aim of this work was to study the protective role of Rose Bengal against Tau aggregation and cytoskeleton modulations. The aggregation inhibition and disaggregation potency of Rose Bengal and photo-excited Rose Bengal were observed by in-vitro fluorescence, circular dichroism, and electron microscopy. Rose Bengal and photo-excited Rose Bengal induce minimal cytotoxicity in neuronal cells. In our studies, we observed that Rose Bengal and photo-excited Rose Bengal modulate the cytoskeleton network of actin and tubulin. The immunofluorescence studies showed the increased filopodia structures after photo-excited Rose Bengal treatment. Furthermore, Rose Bengal treatment increases the connections between the cells. Rose Bengal and photo-excited Rose Bengal treatment-induced actin-rich podosome-like structures associated with cell membranes. The in-vivo studies on UAS E-14 Tau mutant Drosophila suggested that exposure to Rose Bengal and photo-excited Rose Bengal efficiency rescues the behavioural and memory deficit in flies. Thus, the overall results suggest that Rose Bengal could have a therapeutic potency against Tau aggregation.
Topics: Alzheimer Disease; Animals; Cell Line; Cytoskeleton; Drosophila Proteins; Drosophila melanogaster; Humans; Neurons; Photochemotherapy; Protein Aggregation, Pathological; Rose Bengal; tau Proteins
PubMed: 32704015
DOI: 10.1038/s41598-020-69403-2 -
Molecules (Basel, Switzerland) Oct 2022The influence of chitosan (CS) and amphiphilic polymers (AP: pluronic F108 and polyvinylpyrrolidone (PVP)) on the photocatalytic activity of rose bengal (RB) in a model...
The influence of chitosan (CS) and amphiphilic polymers (AP: pluronic F108 and polyvinylpyrrolidone (PVP)) on the photocatalytic activity of rose bengal (RB) in a model reaction of tryptophan photo-oxidation in phosphate-buffered saline (PBS) was studied. It was shown that in the presence of CS, the effective rate constant of tryptophan photo-oxidation catalyzed by RB in PBS solution decreases by a factor of two. This is due to the ionic interaction of the RB with the chitosan. Rose bengal in a slightly acidic environment (pH 4.5) passes into a neutral lactone form, which sharply reduces the photosensitizing properties of the dye. It was demonstrated that the introduction of AP into a solution containing RB and CS prevents direct interaction between RB and CS. This is evidenced by the presence of photocatalytic activity of the dye in the RB-AP-CS systems, as well as bathochromic shifts of the main absorption bands of the dye, and an increase in the optical density and luminescence intensity of the RB when AP is introduced into a buffer solution containing RB and chitosan. The presence of RB-CS and RB-AP interaction in aqueous and PBS media is confirmed by the increase in the degree of fluorescence anisotropy () of these binary systems. In an aqueous solution, the value of for the RB-F108-CS system decreases by a factor of 3.5 (compared to the value of for the RB-CS system), which is associated with the localization of the dye in pluronic micelles. In PBS, the fluorescence anisotropy is practically the same for all systems, which is related to the stability of the dye structure in this medium. The presence of interaction between RB and AP in aqueous solutions was confirmed by the proton NMR method. In addition, the formation of RB-F108 macromolecular complexes, which form associates during solution concentration (in particular, during evaporation), was shown by AFM. Such RB-AP-CS systems may be promising for practical application in the treatment of local foci of infections by aPDT.
Topics: Rose Bengal; Chitosan; Poloxamer; Polymers; Micelles; Povidone; Tryptophan; Protons; Lactones; Phosphates; Photosensitizing Agents
PubMed: 36296390
DOI: 10.3390/molecules27206796