Dual Photosensitizers Research Articles

Dual photosensitizers material for photodynamic theraphy

Abstract Fluoride-based upconversion luminescent materials have the advantage of low phonon energy, which can effectively reduce the non-radiative transition process, so that materials have higher luminous efficiency than other matrix materials. The core–shell NaGdF4:Er3+, Yb3+ @NaGdF4:Tm3+, Yb3+ nanoparticals were synthesized by thermal decomposition method. The core–shell structure can effectively avoid the surface quenching effect, meanwhile, Tm3+ in the shell transmits part of the photons in its excited state to Er3+, effectively enhancing the red emission of Er3+ and improving the luminous efficiency of the samples as a whole. The samples were further coated with a layer of mesoporous silica(mSiO2), where the photosensitizer(PS) Ce6 (red light activated) and MC540 (blue-green light activated) were compounded on through covalent bonds and electrostatic forces, respectively. So that three visable lights include red, green, and blue are all emitted from the sample to activate the PSs to produce reactive oxygen species (ROS) under 980 nm laser irradiation. In cells experiments, the samples were modified with folic acid (FA), which can mediated the cancer cells to target endocytosis. Notable photodynamic therapy (PDT) efficiency was observed under this dual-photosensitizers composite samples for its ROS generation.

Effects of photodynamic therapy using bisdemethoxycurcumin combined with melatonin or acetyl-melatonin on C. Albicans

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT’s antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection.

Cross-linker engineered poly(hydroxyethyl methacrylate) hydrogel allows photodynamic and photothermal therapies and controlled drug release

Here, we disclose the synthesis of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels incorporating a squaraine dye (Sq) as a chemical crosslinker, viz. Sq@PHEMA. Photothermal and photodynamic features of Sq@PHEMA hydrogels are evaluated in detail. It is noteworthy that Sq@PHEMA induces hyperthermia upon irradiation with an 808 nm laser. Furthermore, Sq@PHEMA enables the generation of reactive oxygen species (ROS) upon irradiation with red light. To our delight, Sq@PHEMA hydrogels can be used as efficient dual photosensitizers pertinent to both PDT and PTT simultaneously. Finally, the hydrogels are loaded with methotrexate (MTX) to investigate controlled drug release behavior. It is noted that Sq@PHEMA hydrogels are promising candidates as drug delivery systems since on-demand MTX release is feasible upon irradiation. In summary, we effectively demonstrate that hydrogel cross-linker engineering allows for synergistic photodynamic and photothermal therapy. Furthermore, drug delivery is also feasible with the Sq@PHEMA core.

Synergistic Approaches for Enhanced Light-Driven Hydrogen Production: A Membrane-Anchoring Protein-Engineered Biohybrid System with Dual Photosensitizers Strategy

Synergistic Approaches for Enhanced Light-Driven Hydrogen Production: A Membrane-Anchoring Protein-Engineered Biohybrid System with Dual Photosensitizers Strategy

A hetero-bimetallic Ru(II)-Ir(III) photosensitizer for effective cancer photodynamic therapy under hypoxia.

A hetero-bimetallic Ru(II)-Ir(III) photosensitizer was developed. Upon light exposure, contrary to the homogeneous Ru(II)-Ru(II) and Ir(III)-Ir(III) complexes that can only produce singlet oxygen, Ru(II)-Ir(III) can generate multiple reactive oxygen species and kill hypoxic tumors. This study presents the first example of a hetero-bimetallic type-I and type-II dual photosensitizer.

Dual Photosensitizer Cycles Working Synergistically in a C(sp)‐C(sp3) Cross‐Coupling Reaction**

AbstractTo assess the value and reactivity of new photocatalysts (PCs), their performance should be evaluated in one or more established reactions and benchmarked against the performance using known PCs. Here, we evaluated our recently developed PC, pDTCz‐DPmS, in a C(sp)‐C(sp3) cross‐coupling reaction that had been documented in the literature. Previous findings indicated this reaction could not proceed in the absence of PC; however, under our conditions this was not the case. Without PC, a moderate product yield was obtained, while this yield increased significantly upon addition of pDTCz‐DPmS. UV‐Vis absorption studies indicated that the Hantzsch ester (HE) additive was acting as a competitive absorber of the light from the excitation source, and quenching studies confirmed that the HE was quenched by the radical precursor, N‐(acyloxy)phthalimide. Mechanistic investigations established that two parallel photosensitization pathways were in operation; a reductive quenching photocatalytic pathway (using pDTCz‐DPmS) and a sacrificial photoreductant pathway (employing HE). These pathways work synergistically to enhance the yield of target product.

Dual Photosensitizer Coupled Three‐Dimensional Metal‐Covalent Organic Frameworks for Efficient Photocatalytic Reactions

AbstractIn this work, we innovatively assembled two types of traditional photosensitizers, that is pyridine ruthenium/ferrum (Ru(bpy)32+/Fe(bpy)32+) and porphyrin/metalloporphyrin complex (2HPor/ZnPor) by covalent linkage to get a series of dual photosensitizer‐based three‐dimensional metal‐covalent organic frameworks (3D MCOFs), which behaved strong visible light‐absorbing ability, efficient electron transfer and suitable band gap for highly efficient photocatalytic hydrogen (H2) evolution. Rubpy‐ZnPor COF achieved the highest H2 yield (30 338 μmol g−1 h−1) with apparent quantum efficiency (AQE) of 9.68 %@420 nm, which showed one of the best performances among all reported COF based photocatalysts. Furthermore, the in situ produced H2 was successfully tandem used in the alkyne hydrogenation with ≈99.9 % conversion efficiency. Theoretical calculations reveal that both the two photosensitizer units in MCOFs can be photoexcited and thus contribute optimal photocatalytic activity. This work develops a general strategy and shows the great potential of using multiple photosensitive materials in the field of photocatalysis.

Dual Photosensitizer Coupled Three-Dimensional Metal-Covalent Organic Frameworks for Efficient Photocatalytic Reactions.

In this work, we innovatively assembled two types of traditional photosensitizers, that is pyridine ruthenium/ferrum (Ru(bpy)3 2+ /Fe(bpy)3 2+ ) and porphyrin/metalloporphyrin complex (2HPor/ZnPor) by covalent linkage to get a series of dual photosensitizer-based three-dimensional metal-covalent organic frameworks (3D MCOFs), which behaved strong visible light-absorbing ability, efficient electron transfer and suitable band gap for highly efficient photocatalytic hydrogen (H2 ) evolution. Rubpy-ZnPor COF achieved the highest H2 yield (30 338 μmol g-1 h-1 ) with apparent quantum efficiency (AQE) of 9.68 %@420 nm, which showed one of the best performances among all reported COF based photocatalysts. Furthermore, the in situ produced H2 was successfully tandem used in the alkyne hydrogenation with ≈99.9 % conversion efficiency. Theoretical calculations reveal that both the two photosensitizer units in MCOFs can be photoexcited and thus contribute optimal photocatalytic activity. This work develops a general strategy and shows the great potential of using multiple photosensitive materials in the field of photocatalysis.

Bleeding the Excited State Energy to the Utmost: Single-molecule Iridium Complexes for in Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups have been designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, have been investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrated high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808nm laser irradiation by dual PDT and PTT and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors. This article is protected by copyright. All rights reserved.

Efficient Hydrogen Production by a Photoredox Cascade Catalyst Comprising Dual Photosensitizers and a Transparent Electron Mediator.

One-directional electron transport between a photocatalyst and redox mediator is crucial for achieving highly active Z-scheme water-splitting photocatalysis. Herein, a photoredox cascade catalyst that artificially mimics the electron transport chain in natural photosynthesis was synthesized from a Pt-TiO2 nanoparticle catalyst, two photosensitizers (RuCP6 and RuP6), and a visible-light-transparent electron mediator (HCRu). During photocatalytic hydrogen evolution in the presence of a redox-reversible electron donor, [Co(bpy)3]2+ (bpy = 2,2'-bipyridine), the HCRu-Zr-RuCP6-Zr-RuP6@Pt-TiO2 (PRCC-1) photocatalyst exhibited the highest reported initial (1 h) apparent quantum yield (iAQY = 2.23%) of dye-sensitized TiO2 photocatalysts to date. Furthermore, PRCC-1 successfully produced hydrogen when using hydroquinone monosulfonate (H2QS-) as the hydrogen source.

Chitosan microspheres loaded with 5Fu and Polydopamine-carbon dots for enhancing chemo-photothermal therapy

Herein, Carbon dots (CDS) was modified with polydopamine (PDA), and they were encapsulated using chitosan (CS) to prepare dual photosensitizers drug loaded microspheres ([email protected] + 5Fu NPs). The microsphere has an average particle size of 255 nm and photothermal conversion efficiency of 69.6 % under 808 nm NIR. Notably, the microsphere showed pH and photothermal response drug release performance, contributing to synergistic chemo-photothermal treatment for tumor cells.

Organogold(III) Complexes Display Conditional Photoactivities: Evolving From Photodynamic into Photoactivated Chemotherapy in Response to O2Consumption for Robust Cancer Therapy

AbstractPhotodynamic therapy (PDT) is a spatiotemporally controllable, powerful approach in combating cancers but suffers from low activity under hypoxia, whereas photoactivated chemotherapy (PACT) operates in an O2‐independent manner but compromises the ability to harness O2for potent photosensitization. Herein we report that cyclometalated gold(III)‐alkyne complexes display a PDT‐to‐PACT evolving photoactivity for efficient cancer treatment. On the one hand, the gold(III) complexes can act as dual photosensitizers and substrates, leading to conditional PDT activity in oxygenated condition that progresses to highly efficient PACT (ϕ up to 0.63) when O2is depleted in solution and under cellular environment. On the other hand, the conditional PDT‐to‐PACT reactivity can be triggered by external photosensitizers in a similar manner in vitro and in vivo, giving additional tumor‐selectivity and/or deep tissue penetration by red‐light irradiation that leads to robust anticancer efficacy.

Organogold(III) Complexes Display Conditional Photoactivities: Evolving From Photodynamic into Photoactivated Chemotherapy in Response to O2 Consumption for Robust Cancer Therapy.

Photodynamic therapy (PDT) is a spatiotemporally controllable, powerful approach in combating cancers but suffers from low activity under hypoxia, whereas photoactivated chemotherapy (PACT) operates in an O2 -independent manner but compromises the ability to harness O2 for potent photosensitization. Herein we report that cyclometalated gold(III)-alkyne complexes display a PDT-to-PACT evolving photoactivity for efficient cancer treatment. On the one hand, the gold(III) complexes can act as dual photosensitizers and substrates, leading to conditional PDT activity in oxygenated condition that progresses to highly efficient PACT (ϕ up to 0.63) when O2 is depleted in solution and under cellular environment. On the other hand, the conditional PDT-to-PACT reactivity can be triggered by external photosensitizers in a similar manner in vitro and in vivo, giving additional tumor-selectivity and/or deep tissue penetration by red-light irradiation that leads to robust anticancer efficacy.

A Highly Durable, Self-Photosensitized Mononuclear Ruthenium Catalyst for CO2 Reduction

AbstractA novel mononuclear ruthenium (Ru) complex bearing a PNNP-type tetradentate ligand is introduced here as a self-photosensitized catalyst for the reduction of carbon dioxide (CO2). When the pre-activation of the Ru complex by reaction with a base was carried out, an induction period of catalyst almost disappeared and the catalyst turnover numbers (TONs) over a reaction time of 144 h reached 307 and 489 for carbon monoxide (CO) and for formic acid (HCO2H), respectively. The complex has a long lifespan as a dual photosensitizer and reduction catalyst, due to the sterically bulky and structurally robust (PNNP)Ru framework. Isotope-labeling experiments under 13CO2 atmosphere indicate that CO and HCO2H were both produced from CO2.

Near infrared light activated upconversion nanoparticles (UCNP) based photodynamic therapy of prostate cancers: An in vitro study

Photodynamic therapy (PDT), has a potential to cure cancerous prostate tissue with minimal side effects. Traditional PDT, however, mostly utilized visible (VIS) light range with direct application of hydrophobic photosensitizers which may not be adequate in clinical practice for especially deep-seated cancer cells because of poor penetration of VIS wavelengths. Here, we report near infrared light (NIR) induced and dual photosensitizers (PS) encapsulated PDT strategy to reduce prostate cancer cells - PC3. The designed nanoplatform (MC540/ZnPc-UCNP@Au), in this study, include upconversion nanoparticles (UCNP) synthesis to convert NIR light into multiple VIS wavelengths, porous silica coating to upload dual photosensitizers (MC540/ZnPc), and gold (Au) functionalization to enhance PDT treatment. High chemical stabilization provided MC540/ZnPc-UCNP@Au show excellent biocompatibility, and efficient PDT treatment for prostate cancer cells. In fact, the fluorescence of the synthesized nanoplatforms, upon NIR light excitation, can produce considerable amount of ROS in 5 min, as it is well matched with the absorption of MC540, ZnPc and Au nanoparticles (np). In addition, the easy visualization of cellular internalized/adsorbed nanoplatforms reveal the in situ cell imaging possibility for diagnosis. Based on the evidence of the results, NIR light activated MC540/ZnPc-UCNP@Au may offer a PDT technique for the treatment of prostate cancer.

Novel dual-mode antitumor chlorin-based derivatives as potent photosensitizers and histone deacetylase inhibitors for photodynamic therapy and chemotherapy.

The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy.

Hyaluronic acid wreathed, trio-stimuli receptive and on-demand triggerable nanoconstruct for anchored combinatorial cancer therapy

Hyaluronic acid (HA) assisted effective internalization into CD44 receptor-overexpressing cancer cells, which could offer an excellent cytotoxic profile and tumor alterations. In this study, duo-photothermal agents (copper sulfide (CuS) and graphene oxide (GO)), chemotherapeutic drug (doxorubicin (DOX)), and targeting moiety (HA) were incorporated into a complexed nanoconstruct for trio-responsive chemo-phototherapy. The nanosystem (CuS(DOX)-GO-HA) was demonstrating its responsive drug release and escalated photothermal behavior. The hyperthermia and photodynamic effect were observed along with efficient ROS generation in the presence of dual photosensitizers. The in vivo biodistribution and photothermal profile reflected a high accumulation and retention of the nanoconstruct in the tumor. Importantly, nanoconstructs effectively inhibit tumor growth based on tumor volume analysis and the altered expression of apoptosis, cell proliferation, and angiogenesis markers. Collectively, these findings suggest that this nanoconstruct has excellent antitumor effects in CD44 overexpressed cells showing the potential for clinical translation in the future.

Near-Infrared Light-Triggered Photodynamic Therapy and Apoptosis Using Upconversion Nanoparticles With Dual Photosensitizers.

Elucidation of upconversion nanoparticles (UCNPs) that can be excited by near-infrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nd-doped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.

A Nd3+ sensitized upconversion nanosystem with dual photosensitizers for improving photodynamic therapy efficacy.

The efficacy of photodynamic therapy (PDT) was greatly hindered by the use of a 980 nm laser with undesired overheating effects as well as low reactive oxygen species (ROS) yields. Herein, we address these problems using a dual-photosensitizer (PS) loaded upconversion nanoparticle (UCNP) system. In detail, the NaYF4:Yb/Er/Nd@NaYF4:Nd core-shell UCNP system was designed to exhibit 808 nm laser excitation ability to avoid unfavorable thermal effects. More importantly, the co-encapsulation of dual PS, in terms of merocyanine 540 (MC540) and zinc phthalocyanine (ZnPc), could be respectively triggered by the dual emissions of UCNPs, which could generate sufficient ROS with improved efficiency. Furthermore, in vitro and in vivo studies were conducted to confirm the folate receptor (FR)-overexpressed cancer cell- or tumor-specific targeting ability with minimal side effects on normal tissue, by using this dual PS loaded UCNP system with the modification of the targeting group folic acid (FA). It is worth mentioning that the singlet oxygen production assay and PDT treatment demonstrated significantly enhanced PDT efficacy of the dual-PS approach, in comparison with the single PS method. In short, the FR-targeted dual-PS nanoconstructs maximized the anti-tumor efficacy of PDT by taking advantage of dual fluorescence emission and 808 nm excitation of UCNPs, which might inspire the future development of noninvasive deep-seated tumor treatment.

Targeted Delivery of Functionalized Upconversion Nanoparticles for Externally Triggered Photothermal/Photodynamic Therapies of Brain Glioblastoma.

Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work.Methods: The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers. The hybrid nanoparticles (ANG-IMNPs) were characterized by DLS, TEM, UV/vis and fluorescence spectrophotometer. Cellular uptake was examined by laser scanning confocal microscopy and flow cytometry. The PDT/PTT effect of ANG-IMNPs was evaluated using MTT assay. Tumor accumulation of NPs was determined by a non-invasive in vivo imaging system (IVIS). The in vivo anti-glioma effect of ANG-IMNPs was evaluated by immunohistochemical (IHC) examination of tumor tissues and Kaplan-Meier survival analysis.Results: In vitro data demonstrated enhanced uptake of ANG-IMNPs by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered PDT and PTT. In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro, the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC tissue examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days).Conclusion: In vitro and in vivo data strongly indicate that the ANG-IMNPs were capable of selectively delivering dual photosensitizers to brain astrocytoma tumors for effective PDT/PTT in conjugation with a substantially improved median survival. The therapeutic efficacy of ANG-IMNPs demonstrated in this study suggests their potential in overcoming BBB and establishing an effective treatment against GBM.