ABSTRACT
The lipopolyplex, a multicomponent nonviral gene carrier, generally demonstrates superior colloidal stability, reduced cytotoxicity, and high transfection efficiency. In this study, a new concept, photochemical reaction-induced transfection, using photosensitizer (PS)-loaded lipopolyplexes was applied, which led to enhanced transfection and cytotoxic effects by photoexcitation of the photosensitizer. Hypericin, a hydrophobic photosensitizer, was encapsulated in the lipid bilayer of liposomes. The preformed nanosized hypericin liposomes enclosed the linear polyethylenimine (lPEI)/pDNA polyplexes, resulting in the formation of hypericin lipopolyplexes (Hy-LPP). The diameters of Hy-LPP containing 50 nM hypericin and 0.25 µg of pDNA were 185.6 ± 7.74 nm and 230.2 ± 4.60 nm, respectively, measured by dynamic light scattering (DLS) and atomic force microscopy (AFM). Gel electrophoresis confirmed the encapsulation of hypericin and pDNA in lipopolyplexes. Furthermore, in vitro irradiation of intracellular Hy-LPP at radiant exposures of 200, 600, and 1000 mJ/cm2 was evaluated. It demonstrated 60- to 75-fold higher in vitro luciferase expression than that in nonirradiated cells. The lactate dehydrogenase (LDH) assay supported that reduced transfection was a consequence of photocytotoxicity. The developed photosensitizer-loaded lipopolyplexes improved the transfection efficiency of an exogenous gene or induced photocytotoxicity; however, the frontier lies in the applied photochemical dose. The light-triggered photoexcitation of intracellular hypericin resulted in the generation of reactive oxygen species (ROS), leading to photoselective transfection in HepG2 cells. It was concluded that the two codelivered therapeutics resulted in enhanced transfection and a photodynamic effect by tuning the applied photochemical dose.
Subject(s)
Anthracenes , Carcinoma, Hepatocellular , Liposomes , Liver Neoplasms , Perylene , Photosensitizing Agents , Transfection , Perylene/chemistry , Perylene/analogs & derivatives , Perylene/pharmacology , Anthracenes/chemistry , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Transfection/methods , Liposomes/chemistry , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/pathology , Hep G2 Cells , DNA/chemistry , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Plasmids/chemistry , Cell Survival/drug effectsABSTRACT
BRCA1 gene and carcinoembryonic antigen (CEA) are important markers of breast cancer, so accurate detection of them is significant for early detection and diagnosis of breast cancer. In this study, a potential-resolved ratio electrochemiluminescence (ECL) biosensor using perylene diimide (PDI)-metal-organic framework and DNA nanoflowers (NFs)-CdS quantum dots (QDs) was constructed for detection of BRCA1 and CEA. Specifically, PDI-MOF and CdS QDs can generate potential-resolved intense ECL signals only using one coreactant, so the detection procedure can be effectively simplified. PDI-MOF was first attached to the electrode by graphene oxide, and the dopamine (DA) probe was linked to quench the ECL signal by DNA hybridization. In the presence of target BRCA1, it can form a bipedal DNA walker, so the quenching molecules (DA) were detached from the electrode via the walker amplification process aided by Mg2+, so that the PDI signal at -0.25 V was restored for the BRCA1 assay. Moreover, CdS QDs@DNA NFs as amplified signal probes were formed by self-assembly, and the target CEA-amplified product introduced the CdS QDs@DNA NFs to the electrode, so the QD ECL signal at -1.42 V was enhanced, while the ECL signal of PDI is unchanged; thus, CEA detection was achieved by the ratio value between them. Therefore, the detection accuracy is guaranteed by detection of two cancer markers and a ratio value. This biosensor has a great contribution to the development of new ECL materials and a novel ECL technique for fast and efficient multitarget assays, showing great significance for the early monitoring and diagnosis of breast cancer.
Subject(s)
BRCA1 Protein , Biosensing Techniques , Cadmium Compounds , Carcinoembryonic Antigen , DNA , Electrochemical Techniques , Imides , Luminescent Measurements , Perylene , Quantum Dots , Sulfides , Perylene/chemistry , Perylene/analogs & derivatives , Quantum Dots/chemistry , Cadmium Compounds/chemistry , Biosensing Techniques/methods , Sulfides/chemistry , Electrochemical Techniques/methods , Imides/chemistry , DNA/chemistry , Humans , BRCA1 Protein/genetics , BRCA1 Protein/analysis , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/blood , Metal-Organic Frameworks/chemistryABSTRACT
Chirality is one of the hallmarks of biomolecules. Herein, we utilize heparin, a chiral biomolecule and potent drug, to induce chiral organization into the assembly of an achiral molecule. Polyanionic heparin binds with a dicationic perylenediimide derivative to induce supramolecular helical organization in aqueous medium as well as in a highly competitive cell culture medium.
Subject(s)
Heparin , Imides , Perylene , Heparin/chemistry , Imides/chemistry , Perylene/chemistry , Perylene/analogs & derivatives , Stereoisomerism , Humans , Molecular Structure , Macromolecular Substances/chemistry , Macromolecular Substances/chemical synthesisABSTRACT
To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.
Subject(s)
Alginates , Anthracenes , Nanoparticles , Perylene , Silicon Dioxide , Tirapazamine , Tumor Microenvironment , Silicon Dioxide/chemistry , Tumor Microenvironment/drug effects , Alginates/chemistry , Animals , Humans , Tirapazamine/chemistry , Tirapazamine/pharmacology , Nanoparticles/chemistry , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Mice , Anthracenes/chemistry , Cell Line, Tumor , Photochemotherapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Drug Delivery Systems , Drug Liberation , Porosity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Drug Synergism , Nanoparticle Drug Delivery System/chemistryABSTRACT
Nanofibers have emerged as a highly effective method for drug delivery, attributed to their remarkable porosity and ability to regulate drug release rates while minimizing toxicity and side effects. In this study, we successfully loaded the natural anticancer drugs curcumin (CUR) and hypocrellin A (HA) into pure poly(l-lactic acid) (PLLA) and PLLA-silk protein (PS) composite nanofibers through electrospinning technology. This result was confirmed through comprehensive analysis involving SEM, FTIR, XRD, DSC, TG, zeta potential, and pH stability analysis. The encapsulation efficiency of all samples exceeded 85%, demonstrating the effectiveness of the loading process. Additionally, the drug release doses were significantly higher in the composites compared to pure PLLA, owing to the enhanced crystallinity and stability of the silk proteins. Importantly, the composite nanofibers exhibited excellent pH stability in physiological and acidic environments. Furthermore, the drug-loaded composite nanofibers displayed strong inhibitory effects on cancer cells, with approximately 28% (HA) and 37% (CUR) inhibition of cell growth and differentiation within 72 h, while showing minimal impact on normal cells. This research highlights the potential for controlling drug release through the manipulation of fiber diameter and crystallinity, paving the way for wider applications of electrospun green nanomaterials in the field of medicine.
Subject(s)
Antineoplastic Agents , Cell Proliferation , Curcumin , Drug Liberation , Drug Screening Assays, Antitumor , Fibroins , Nanofibers , Particle Size , Perylene , Phenol , Polyesters , Quinones , Curcumin/chemistry , Curcumin/pharmacology , Nanofibers/chemistry , Fibroins/chemistry , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Polyesters/chemistry , Quinones/chemistry , Quinones/pharmacology , Cell Proliferation/drug effects , Phenol/chemistry , Perylene/chemistry , Perylene/analogs & derivatives , Perylene/pharmacology , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Delayed-Action Preparations/chemistry , Cell Survival/drug effects , Cell Line, TumorABSTRACT
Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents , Fluorescent Dyes , Perylene , Spectrometry, Fluorescence , Surface-Active Agents , Surface-Active Agents/chemistry , Aminoglycosides/chemistry , Aminoglycosides/analysis , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Fluorescent Dyes/chemistry , Humans , Perylene/chemistry , Perylene/analogs & derivatives , Sodium Dodecyl Sulfate/chemistryABSTRACT
Bipolar electrochemical microscopy (BEM), which visualizes the concentration distribution of molecular species in biological systems by electrochemiluminescence (ECL), is expected to be applied to the high-spatiotemporal-resolution imaging of biomolecules, enabling the analysis of cellular functions. In the past, the molecular species that could be imaged by BEM were generally restricted to oxidized molecules due to the limitation derived from the ECL mechanism of the luminophore. Recently, the imaging of dopamine (DA), a reduced molecule, was achieved using Ru (bpy)32+/glutathione disulfide (GSSG) as a cathodic luminophore. However, a large driving voltage was required for ECL generation, resulting in a low S/N ratio. In this study, we employed N,N'-dimethyl-3,4,9,10-perylenetetracarboxylic diimide (PDI-CH3)/potassium peroxodisulfate (K2S2O8), which is a cathodic luminophore that can be reduced at a nobler potential to produce ECL than [Ru(bpy)3]2+/GSSG. First, the ECL mechanism of PDI-CH3/K2S2O8 was elucidated by using a PDI-CH3 drop-cast glassy carbon electrode (GCE) immersed in K2S2O8 solution as the working electrode in a 3-electrode system. The PDI-CH3 drop-casted GCE, a single closed bipolar electrode (c-BPE), was used as the cathode in the successful quantification of 50-500 µmol L-1 DA in a sample chamber in which a c-BPE anode was immersed, resulting in a high S/N. The selective detection of DA in the presence of ascorbic acid was achieved by modifying the anode with Nafion. Finally, DA imaging was demonstrated using a commercially available anisotropic conducting film with PDI-CH3 coating on the cathode surface as a c-BPE array. The change in the concentration distribution in the inflow of DA was successfully imaged based on the change in the ECL intensity at the c-BPE cathode. This BEM system is expected to be useful for DA imaging of the brain.
Subject(s)
Dopamine , Electrochemical Techniques , Electrodes , Imides , Perylene , Dopamine/analysis , Dopamine/chemistry , Perylene/chemistry , Perylene/analogs & derivatives , Imides/chemistry , Electrochemical Techniques/methods , Luminescent Measurements/methods , Sulfates/chemistry , Sulfates/analysis , Potassium CompoundsABSTRACT
Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.
Subject(s)
Anthracenes , Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Perylene , Photochemotherapy , Photosensitizing Agents , Signal Transduction , rho-Associated Kinases , rhoA GTP-Binding Protein , Humans , Perylene/analogs & derivatives , Perylene/pharmacology , Perylene/chemistry , rho-Associated Kinases/metabolism , rho-Associated Kinases/antagonists & inhibitors , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Anthracenes/pharmacology , Signal Transduction/drug effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , rhoA GTP-Binding Protein/metabolism , rhoA GTP-Binding Protein/antagonists & inhibitors , Epithelial-Mesenchymal Transition/drug effects , Cell Movement/drug effects , Neoplasm Metastasis , Drug Screening Assays, AntitumorABSTRACT
Breast adenocarcinoma ranks high among the foremost lethal cancers affecting women globally, with its triple-negative subtype posing the greatest challenge due to its aggressiveness and resistance to treatment. To enhance survivorship and patients' quality of life, exploring advanced therapeutic approaches beyond conventional chemotherapies is imperative. To address this, innovative nanoscale drug delivery systems have been developed, offering precise, localized, and stimuli-triggered release of anticancer agents. Here, we present perylenemonoimide nanoparticle-based vehicles engineered for deep-red light activation, enabling direct chlorambucil release. Synthesized via the reprecipitation technique, these nanoparticles were thoroughly characterized. Light-induced drug release was monitored via spectroscopic and reverse-phase HPLC. The efficacy of the said drug delivery system was evaluated in both two-dimensional and three-dimensional spheroidal cancer models, demonstrating significant tumor regression attributed to apoptotic cell death induced by efficient drug release within cells and spheroids. This approach holds promise for advancing targeted breast cancer therapy, enhancing treatment efficacy and minimizing adverse effects.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Spheroids, Cellular , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Spheroids, Cellular/drug effects , Drug Liberation , Light , Chlorambucil/chemistry , Chlorambucil/pharmacology , Chlorambucil/therapeutic use , Nanoparticles/chemistry , Cell Line, Tumor , Apoptosis/drug effects , Photons , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Perylene/therapeutic use , Red LightABSTRACT
BACKGROUND: The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer has already been proved, the availability is still limited. Hypericin, a naphthodianthrone isolated essentially from plant source Hypericum perforatum L. along with other related anthraquinones and bisanthraquinones belongs to this group of compounds. Although it has been proven that hypericin is synthesized by the polyketide pathway in plants, none of the candidate genes coding for key enzymes has been experimentally validated yet. Despite the rare occurrence of anthraquinones in plants, their presence in microorganisms, including endophytic fungi, is quite common. Unlike plants, several biosynthetic genes grouped into clusters (BGCs) in fungal endophytes have already been characterized. RESULTS: The aim of this work was to predict, identify and characterize the anthraquinone BGCs in de novo assembled and functionally annotated genomes of selected endophytic fungal isolates (Fusarium oxysporum, Plectosphaerella cucumerina, Scedosporium apiospermum, Diaporthe eres, Canariomyces subthermophilus) obtained from different tissues of Hypericum spp. The number of predicted type I polyketide synthase (PKS) BGCs in the studied genomes varied. The non-reducing type I PKS lacking thioesterase domain and adjacent discrete gene encoding protein with product release function were identified only in the genomes of C. subthermophilus and D. eres. A candidate bisanthraquinone BGC was predicted in C. subthermophilus genome and comprised genes coding the enzymes that catalyze formation of the basic anthraquinone skeleton (PKS, metallo-beta-lactamase, decarboxylase, anthrone oxygenase), putative dimerization enzyme (cytochrome P450 monooxygenase), other tailoring enzymes (oxidoreductase, dehydrogenase/reductase), and non-catalytic proteins (fungal transcription factor, transporter protein). CONCLUSIONS: The results provide an insight into genetic background of anthraquinone biosynthesis in Hypericum-borne endophytes. The predicted bisanthraquinone gene cluster represents a basis for functional validation of the candidate biosynthetic genes in a simple eukaryotic system as a prospective biotechnological alternative for production of hypericin and related bioactive anthraquinones.
Subject(s)
Anthraquinones , Endophytes , Hypericum , Multigene Family , Polyketides , Hypericum/microbiology , Hypericum/genetics , Hypericum/metabolism , Polyketides/metabolism , Endophytes/genetics , Endophytes/metabolism , Anthraquinones/metabolism , Fungi/genetics , Genome, Fungal , Computer Simulation , Polyketide Synthases/genetics , Perylene/analogs & derivatives , Perylene/metabolism , Anthracenes/metabolism , Genomics , PhylogenyABSTRACT
In this study, Fe3O4 nanoparticles (FeNPs) decorated with halogenated perylene diimides (PDIs) have been used for capturing VOCs (volatile organic compounds) through noncovalent binding. Concretely, we have used tetrachlorinated/brominated PDIs as well as a nonhalogenated PDI as a reference system. On the other hand, methanol, ethanol, propanol, and butanol were used as VOCs. Experimental studies along with theoretical calculations (the BP86-D3/def2-TZVPP level of theory) pointed to two possible and likely competitive binding modes (lone pair-π through the π-acidic surface of the PDI and a halogen bond via the σ-holes at the Cl/Br atoms). More in detail, thermal desorption (TD) experiments showed an increase in the VOC retention capacity upon increasing the length of the alkyl chain, suggesting a preference for the interaction with the PDI aromatic surface. In addition, the tetrachlorinated derivative showed larger VOC retention times compared to the tetrabrominated analog. These results were complemented by several state-of-the-art computational tools, such as the electrostatic surface potential analysis, the Quantum Theory of Atoms in Molecules (QTAIM), as well as the noncovalent interaction plot (NCIplot) visual index, which were helpful to rationalize the role of each interaction in the VOC···PDI recognition phenomena.
Subject(s)
Alcohols , Alcohols/chemistry , Perylene/chemistry , Perylene/analogs & derivatives , Volatile Organic Compounds/chemistry , Halogens/chemistry , Magnetite Nanoparticles/chemistry , Quantum TheoryABSTRACT
BACKGROUND: Conventional topical psoriasis treatments suffer from limited delivery to affected areas and skin irritation due to high local drug concentration. PURPOSE: This study aims to prepare hypericin (HYP) loaded nanostructured lipid carriers (NLCs) and their application in psoriasis treatment through intradermal administration using hollow microneedles assisted by photodynamic therapy. METHODS: The colloidal characteristics of NLCs, entrapment efficiency and morphology were evaluated. An ex-vivo skin distribution study was conducted along with testing the in vivo antipsoriatic activity in mice with the imiquimod-induced psoriasis model. RESULTS: The particle size and zeta potential of HYP-NLCs were 167.70 nm and -18.1, respectively. The ex-vivo skin distribution study demonstrated the superior distribution of HYP-NLCs to a depth of 1480 µm within the skin layers relative to only 750 µm for free HYP. In vivo studies revealed that the levels of NF-KB, IL 6, MMP1, GSH, and catalase in the group treated with HYP-NLCs in the presence of light were comparable to the negative control. CONCLUSIONS: The histopathological inspection of dissected skin samples reflected the superiority of HYP-NLCs over HYP ointment. This could be ascribed to the effect of nanoencapsulation on improving HYP properties besides the ability of hollow microneedles to ensure effective HYP delivery to the affected psoriatic area.
Subject(s)
Anthracenes , Imiquimod , Needles , Perylene , Photochemotherapy , Psoriasis , Psoriasis/drug therapy , Psoriasis/chemically induced , Animals , Imiquimod/administration & dosage , Perylene/analogs & derivatives , Perylene/administration & dosage , Perylene/pharmacology , Photochemotherapy/methods , Mice , Administration, Cutaneous , Drug Delivery Systems , Lipids/chemistry , Drug Carriers/chemistry , Photosensitizing Agents/administration & dosage , Particle Size , Skin/metabolism , Skin/pathology , Male , Mice, Inbred BALB C , Nanostructures , Disease Models, AnimalABSTRACT
Perylenequinones (PQs) are natural photosensitizing compounds used as photodynamic therapy, and heat stress (HS) is the main limiting factor of mycelial growth and secondary metabolism of fungi. This study aimed to unravel the impact of HS-induced Ca2+ and the calcium signaling pathway on PQ biosynthesis of Shiraia sp. Slf14(w). Meanwhile, the intricate interplay between HS-induced NO and Ca2+ and the calcium signaling pathway was investigated. The outcomes disclosed that Ca2+ and the calcium signaling pathway activated by HS could effectively enhance the production of PQs in Shiraia sp. Slf14(w). Further investigations elucidated the specific mechanism through which NO signaling molecules induced by HS act upon the Ca2+/CaM (calmodulin) signaling pathway, thus propelling PQ biosynthesis in Shiraia sp. Slf14(w). This was substantiated by decoding the downstream positioning of the CaM/CaN (calcineurin) pathway in relation to NO through comprehensive analyses encompassing transcript levels, enzyme assays, and the introduction of chemical agents. Concurrently, the engagement of Ca2+ and the calcium signaling pathway in heat shock signaling was also evidenced. The implications of our study underscore the pivotal role of HS-induced Ca2+ and the calcium signaling pathway, which not only participate in heat shock signal transduction but also play an instrumental role in promoting PQ biosynthesis. Consequently, our study not only enriches our comprehension of the mechanisms driving HS signaling transduction in fungi but also offers novel insights into the PQ synthesis paradigm within Shiraia sp. Slf14(w). KEY POINTS: ⢠The calcium signaling pathway was proposed to participate in PQ biosynthesis under HS. ⢠HS-induced NO was revealed to act upon the calcium signaling pathway for the first time.
Subject(s)
Ascomycota , Calcium Signaling , Perylene , Perylene/analogs & derivatives , Quinones , Ascomycota/metabolism , Ascomycota/genetics , Ascomycota/growth & development , Quinones/metabolism , Perylene/metabolism , Nitric Oxide/metabolism , Heat-Shock Response , Calcium/metabolism , Hot TemperatureABSTRACT
Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2â¢- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.
Subject(s)
Imides , Optical Imaging , Perylene , Photochemotherapy , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Perylene/therapeutic use , Imides/chemistry , Imides/therapeutic use , Photochemotherapy/methods , Humans , Optical Imaging/methods , Animals , Mice , Fluorescent Dyes/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Photothermal Therapy , Infrared Rays , Cell Line, TumorABSTRACT
An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.
Subject(s)
Manganese Compounds , Nanoparticles , Oxides , Perylene , Photochemotherapy , Photosensitizing Agents , Quinones , Photochemotherapy/methods , Perylene/analogs & derivatives , Perylene/pharmacology , Perylene/chemistry , Perylene/administration & dosage , Humans , Quinones/chemistry , Quinones/pharmacology , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Oxides/chemistry , Oxides/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/administration & dosage , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Animals , Phenol/chemistry , Phenol/pharmacology , Liposomes/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Mice , Cell Line, Tumor , Tumor Microenvironment/drug effectsABSTRACT
Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 µM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Longevity , Oxidative Stress , Perylene , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Transcription Factors , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , Oxidative Stress/drug effects , Longevity/drug effects , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Perylene/analogs & derivatives , Perylene/pharmacology , Anthracenes/pharmacology , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Gene Expression Regulation/drug effects , Light , Acetylcysteine/pharmacologyABSTRACT
Plant-pathogenic fungi produce toxins as virulence factors in many plant diseases. In Cercospora leaf blight of soybean caused by Cercospora cf. flagellaris, symptoms are a consequence of the production of a perylenequinone toxin, cercosporin, which is light-activated to produce damaging reactive oxygen species. Cercosporin is universally toxic to cells, except to the cells of the producer. The current model of self-resistance to cercosporin is largely attributed to the maintenance of cercosporin in a chemically reduced state inside hyphae, unassociated with cellular organelles. However, in another perylenequinone-producing fungus, Phaeosphaeria sp., the toxin was specifically sequestered inside lipid droplets (LDs) to prevent reactive oxygen species production. This study hypothesized that LD-based sequestration of cercosporin occurred in C. cf. flagellaris and that lipid-inhibiting fungicides could inhibit toxin production. Confocal microscopy using light-cultured C. cf. flagellaris indicated that 3-day-old hyphae contained two forms of cercosporin distributed in two types of hyphae. Reduced cercosporin was uniformly distributed in the cytoplasm of thick, primary hyphae, and, contrary to previous studies, active cercosporin was observed specifically in the LDs of thin, secondary hyphae. The production of hyphae of two different thicknesses, a characteristic of hemibiotrophic plant pathogens, has not been documented in C. cf. flagellaris. No correlation was observed between cercosporin production and total lipid extracted, and two lipid-inhibiting fungicides had little effect on fungal growth in growth-inhibition assays. This study lays a foundation for exploring the importance of pathogen lifestyle, toxin production, and LD content in the pathogenicity and symptomology of Cercospora.
Subject(s)
Cercospora , Hyphae , Perylene , Plant Diseases , Perylene/analogs & derivatives , Perylene/metabolism , Plant Diseases/microbiology , Hyphae/drug effects , Hyphae/growth & development , Cercospora/metabolism , Glycine max/microbiology , Ascomycota/drug effects , Ascomycota/physiology , Ascomycota/growth & development , Ascomycota/metabolism , Reactive Oxygen Species/metabolism , Fungicides, Industrial/pharmacology , Lipid Droplets/metabolism , Plant Leaves/microbiology , Microscopy, ConfocalABSTRACT
In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 µg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field.
Subject(s)
Anthracenes , Anti-Bacterial Agents , Disulfides , Drug Carriers , Escherichia coli , Perylene , Photochemotherapy , Polyethylene Glycols , Reactive Oxygen Species , Silicon Dioxide , Staphylococcus aureus , Perylene/analogs & derivatives , Perylene/chemistry , Perylene/pharmacology , Anthracenes/chemistry , Polyethylene Glycols/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Silicon Dioxide/chemistry , Staphylococcus aureus/drug effects , Porosity , Reactive Oxygen Species/metabolism , Drug Carriers/chemistry , Disulfides/chemistry , Hemolysis/drug effects , Humans , Animals , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistryABSTRACT
The quantitative analysis of multicomponents by single-marker(QAMS) was established for 13 chemical components of Epimedii Folium, including neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â , so as to investigate the feasibility and accuracy of this method in evaluating the quality of Epimedii Folium materials from different origins and different varieties. Through the scientific and accurate investigation of the experimental method, the external standard method was used to determine the content of 13 chemical components in epimedium brevieornu. At the same time, icariin was used as the internal standard, and the relative correction factors of icariin with neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â were established, respectively. The contens of neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuosideâ in Epimedii Folium were calculated by QAMS. Finally, the difference between the measured value and the calculated value was compared to verify the accuracy and scientific nature of QAMS in the determination. The relative correction factor of each component had better repeatability, and there was no significant difference between the results of the external standard method and those of QAMS. With icariin as the internal standard, QAMS simultaneously determining neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â can be used for quantitative analysis of Epimedii Folium.
Subject(s)
Anthracenes , Drugs, Chinese Herbal , Epimedium , Perylene/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Chlorogenic Acid , Flavonoids/analysis , Drugs, Chinese Herbal/chemistry , Epimedium/chemistryABSTRACT
Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.