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Photodynamic therapy (PDT) involves the activation of photosensitizers (PSs) by visible laser light at the target site to catalyze the production of reactive oxygen species, resulting in tumor cell death and blood vessel closure. The efficacy of PDT depends on the PSs, the amount of oxygen, and the intensity of the excitation laser. PSs have been extensively researched, and great efforts have been made to develop an ideal photosensitizer. Chlorin-e6 is an FDA-approved second-generation PSs that has attracted widespread research interest in the medical field, especially with respect to antitumor and anti-inflammatory activity. Chlorin-e6 possesses the advantages of a large absorption coefficient, high strength, low residue in the body, and relatively high safety and thus has promising application prospects. Here we review the use of chlorin-e6 in PDT and discuss the prospects of further development of this technology. [ABSTRACT FROM AUTHOR]

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to the therapeutic efficacy of the process. Chlorin e6 is a second-generation photosensitizer, approved by the FDA with the most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity is a major limitation, leading to poor biodistribution. To overcome this condition, the present work developed an up-to-date nanoemulsion incorporating Ce6 in a new nanosystem (Ce6/NE). A comprehensive study of physicochemical properties, stability, fluorescence characteristics, the in vitro release profile, in vivo and ex vivo biocompatibility, and ex vivo efficacy was established. The nanoemulsions showed the desired particle size and stability over six months, with no spectroscopic or photophysical alterations. Uptake studies demonstrated the internalization of the Ce6/NE in monolayers, with biocompatibility at the lowest concentrations. The HET-CAM assay, however, revealed a higher biocompatibility range, also indicating Ce6/NE's potential for cancer treatment through antiangiogenic studies. These findings highlight the use of a new promising photosensitizer for PDT modulated with nanotechnology that promotes low toxicity, higher bioavailability, and site-specific delivery. [ABSTRACT FROM AUTHOR]

We use phototherapy rather than chemotherapy and radiotherapy for the first time before surgery to thoroughly remove the tumors with minimum wound area and few side effects. The phototoxicity under hypoxia conditions and targeting ability of photosensitizers were improved by camouflaging Chlorin e6 and chlorambucil assemblies with cancer cell membranes. This work provides a creative method for tumor clinical therapy. [Display omitted] Surgical risk and wound area can be reduced by diminishing tumor volume before surgery. The chemotherapy and radiotherapy currently used that can reduce the tumor volume generally cause severe systemic side effects. Phototherapy has recently emerged as an effective treatment modality for superficial cancers. However, phototherapy is limited by the low utilization of photosensitizer, the tumor hypoxia, and the low photothermal conversion efficiency. Herein, we report the cancer membrane biomimetic nanoparticles assembled by Chlorin e6 (Ce6) and chlorambucil (CRB). Ce6@CRB nanoparticles (CCNPs) show excellent photothermal conversion efficiency, which is 2 times higher than free Ce6. Meanwhile, CCNPs can produce singlet oxygen stably compared to free Ce6 thereby reducing the dependence on oxygen. Furthermore, the coating of 4 T1 cancer membrane on the surface of CCNPs endows them with the ability of homologous targeting, not only improving the utilization of Ce6, but also effectively activating the immune system in vivo when combined photodynamic therapy (PDT) and photothermal therapy (PTT). Intriguingly, surgical resection is performed after phototherapy in this treatment regimen, which can effectively reduce the wound area. Together, this work provided a feasible and creative method for tumor clinical therapy for its patient-centric and humanitarian focus. [ABSTRACT FROM AUTHOR]

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666 nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT), as a non-invasive and selective treatment strategy, has garnered extensive research interest. Photothermal agents (PTAs) are critical components of PTT, whose light-absorbing and thermosensitive properties enable effective conversion of light energy into heat, creating localized high-temperature regions. However, PTAs often face challenges with degradation in vivo, and standalone PTT is insufficient for complete tumor cell ablation. In this study, we successfully developed a biodegradable nanoplatform for synergistic photothermal-photodynamic therapy. This platform is based on degradable antimonene nanosheets, further functionalized with a chitosan coating, and loaded with the photosensitizer Ce6. In vitro experiments demonstrated that this nanoplatform exhibits excellent biocompatibility and biodegradability. Upon laser excitation, the platform induces localized thermal effects for cell ablation and promotes reactive oxygen species generation, leading to superior anti-tumor efficacy compared to monotherapies. These findings suggest that this multifunctional nanoplatform can significantly enhance the therapeutic efficiency of synergistic phototherapy, presenting a promising candidate for cancer treatment. [ABSTRACT FROM AUTHOR]

Nanotechnology is an emerging field that involves the development of nanoscale particles, their fabrication methods, and potential applications. From nanosized inorganic particles to biopolymers, the variety of nanoparticles is unstoppably growing, offering huge opportunities for drug delivery. Various nanoformulations, such as nanoparticles, nanocomposites, and nanoemulsions, have been developed to enhance drug stability, solubility, and tissue penetration. Moreover, nanocarriers can be specifically engineered to target diseased cells or release the drug in a controllable manner, minimizing damage to surrounding healthy tissues and reducing side effects. This review focuses on the combinations between porphyrin derivatives and nanocarriers applied in photodynamic therapy (PDT). PDT has emerged as a significant advance in medicine, offering a low-invasive method for managing infections, the treatment of tumors, and various dermatoses. The therapy relies on the activation of a photosensitizer by light, which results in the generation of reactive oxygen species. Despite their favorable properties, porphyrins reveal non-specific distribution within the body. Nanotechnology has the capability to enhance the PS delivery and its activation. This review explores the potential improvements that are provided by the use of nanotechnology in the PDT field. [ABSTRACT FROM AUTHOR]

The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with the amine group of chitosan oligosaccharide (COS) using a thioketal linker (COSthBSO) to liberate BSO and chlorine e6 (Ce6) under oxidative stress, and then, Ce6-COSthBSO NP (Ce6-COSthBSO NP), fabricated by a dialysis procedure, showed an accelerated release rate of BSO and Ce6 by the addition of hydrogen peroxide, indicating that nanophotosensitizers have ROS sensitivity. In the in vitro cell culture study using HCT116 colon carcinoma cells, a combination of BSO and Ce6 efficiently suppressed the intracellular GSH and increased ROS production compared to the sole treatment of Ce6. In particular, Ce6-COSthBSO NP showed higher efficacy in the suppression of GSH levels and ROS production compared to the free Ce6 and Ce6/BSO combination. These results were due to the fact that Ce6-COSthBSO NP was efficiently delivered to the intracellular region, suppressed intracellular GSH levels, and elevated ROS levels. The in vivo animal tumor xenograft study demonstrated Ce6-COSthBSO NP being efficiently delivered to the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was higher than those of other organs. The combination of Ce6 and BSO efficiently suppressed tumor growth compared to the sole treatment of Ce6, indicating that BSO might efficiently suppress GSH levels and increase ROS levels in the tumor microenvironment. Specifically, Ce6-COSthBSO NP showed the strongest performance in inhibition of tumor growth than those of Ce6 or the CE6/BSO combination, indicating that they were efficiently delivered to tumor tissue, increased ROS levels, and then efficiently inhibited tumor growth. We suggest that COSthBSO nanophotosensitizers are promising candidates for PDT treatment of cancer cells. [ABSTRACT FROM AUTHOR]

Different types of photosensitizers (PSs) have different dynamics and intensities of accumulation, depending on the type of tumor or different areas within the same tumor. This determines the effectiveness of fluorescence diagnostics and photodynamic therapy (PDT). This paper studies the processes of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) and chlorin e6 (Ce6) accumulation in the central and border zones of a tumor after combined administration of two PSs into the patient's body. Fluorescence diagnostic methods have shown that sublingual administration of 5-ALA leads to the more intense accumulation of PpIX in a tumor compared to oral administration. Differences have been identified in the dynamics of 5-ALA-induced PpIX and Ce6 accumulation in the central and border zones of the tumor, as well as normal tissues. Ce6 accumulates mainly in the central zone of the tumor while PpIX accumulates in the border zone of the tumor. All patients with combined PDT experienced complete therapeutic pathomorphosis and relapse-free observation. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption–desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m−2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation. [ABSTRACT FROM AUTHOR]

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis. [ABSTRACT FROM AUTHOR]

Functional passivation agents have been shown to effectively optimize the crystallization process and passivate defects on the surface and grain boundaries. People have conducted extensive research on the passivation mechanisms of various passivation agents to obtain more effective passivation agents. Researchers are gradually focusing on natural ingredients in the search for suitable passivation agents due to the wide variety, green color, and ease of production. As a result, the natural chlorophyll component chlorin e6 (CE‐6) is first combined with perovskite solar cells (PSCs) to improve their performance. Following the incorporation of CE‐6 into the perovskite layer, various functional groups of CE‐6 are used to effectively reduce traps on the perovskite surface, suppress charge recombination at the interface, improve carrier transfer rate and carrier extraction efficiency, and ultimately improve efficiency. The optimal device achieves a power conversion efficiency (PCE) of 21.14% and maintains its initial PCE of 84% after being stored in a room‐temperature air environment for 500 h. Furthermore, semitransparent PSC (ST‐PSC) is made with 13.33% PCE and 5.53% average visible light transmittance. The findings show that natural material CE‐6 performs well in the perovskite layer and confirms the promising prospects for optimizing ST‐PSC. [ABSTRACT FROM AUTHOR]

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities. [ABSTRACT FROM AUTHOR]

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 μM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV–visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M−1 and 2.35 × 1012 M−2, respectively, using B–H (Benesi–Hildebrand) plots. Fluorescence lifetimes, B–H plots, FT–IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule. [ABSTRACT FROM AUTHOR]

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies. [ABSTRACT FROM AUTHOR]

In this study, we developed macrophage-derived nanovesicles (MNVs) to specifically target tumor cells. Initially, we chemically coupled hyaluronic acid (HA) with 3-(diethylamino)propylamine (DEAP; with a pKb value of approximately 7.0) to confer pH-responsive properties. The resulting polymer (HDEA) and chlorin e6 (Ce6, serving as a photosensitizing model drug) were incorporated into MNVs using a sonication process, resulting in Ce6-loaded HDEA@MNVs. Our experiments demonstrated that the integrin α4β1 expressed in MNVs selectively interacted with vascular cell adhesion molecule-1 (VCAM-1) in SK-N-MC tumor cells, leading to enhanced accumulation of MNVs within the tumor cells. Consequently, HDEA@MNVs exhibited significant accumulation within tumor cells, underwent structural destabilization at endosomal pH due to the protonation of pH-responsive DEAP within the HDEA@MNVs, and facilitated the release of Ce6. The released free Ce6 from MNVs exhibited improved effectiveness in photodynamic tumor therapy when exposed to laser irradiation. In vitro cell experiments demonstrated efficient internalization of HDEA@MNVs into tumor cells and high efficacy in photodynamic therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Photodynamic therapy (PDT) using photosensitisers is a minimally invasive treatment for malignant tumours. However, ideal photosensitisers are not yet established. Recently, we developed a new photosensitiser, glucose‐conjugated chlorin e6 (G‐Ce6). Objectives To evaluate the clinical efficacy of vascular‐targeted PDT (VTP), a type of PDT utilising a short drug‐light interval, using G‐Ce6 to treat spontaneously occurring tumours in dogs. Methods Five dogs with spontaneously occurring tumours (malignant melanoma: three; haemangiopericytoma: two; and squamous cell carcinoma: one) were subjected to VTP. These dogs were intravenously injected with G‐Ce6 at doses of 1–3 mg/kg 5 min before laser irradiation. Tumours were superficially or interstitially irradiated using a 677‐nm diode laser. Results Repeated VTP decreased tumour size, yielding complete remission in three dogs. Complications such as oedema surrounding normal tissues and fistulae were observed, and the oedema was self‐limiting. The fistula was cured by debriding the necrotic tissues formed after VTP. Conclusions Our findings demonstrate that VTP using G‐Ce6 had antitumour effects in dogs with spontaneously occurring tumours.

Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity. Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO3 particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method. Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6. Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug’s free form. Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

In this paper, a metal–organic skeleton material MIL‐101‐NH2‐AL was prepared for loading the chemotherapeutic drug Oridonin (Ori) and photosensitizer Chlorin e6 (Ce6). A drug delivery system for synergistic chemotherapy and photodynamic therapy was constructed. At the same time, we evaluated MIL‐101‐NH2‐AL as a drug therapy carrier, including drug loading, cytotoxicity, and safety, verified the photodynamic efficiency of MIL‐101‐NH2‐AL@Ori@Ce6 in vitro, and studied the ability of MIL‐101‐NH2‐AL@Ori@Ce6 cancer cells to produce reactive oxygen species, cell uptake, cytotoxicity, and so on. Experiments have confirmed that MIL‐101‐NH2‐AL, as a nano‐carrier, encapsulated Oridonin and Ce6, the combination of PDT and chemotherapy showed enhanced tumor inhibition and high biosafety. The killing effect on cells was caused by reactive oxygen species produced by photosensitizers and apoptosis of tumor cells induced by Oridonin. The drug delivery system demonstrates enormous potential for synergistic anti‐tumor effects of photodynamic and chemotherapy. [ABSTRACT FROM AUTHOR]

Layered magnesium silicate was modified by water-insoluble chlorin e6 derivatives with two and three ethanolamine fragments on the periphery of the macrocycle by introducing chlorin e6 derivatives into the reaction medium as solutions in hydrochloric acid without the use of organic solvents. The modified layered silicates obtained are characterized by intense fluorescence along with photostability and exhibit photochemical activity in reactions of photosensitized oxidation of model pollutants like xanthene (rhodamine 6G) and azo dyes (methyl orange). [ABSTRACT FROM AUTHOR]

Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 17¹- and 15² cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, ¹H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development. [ABSTRACT FROM AUTHOR]

Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA 1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS. [ABSTRACT FROM AUTHOR]

Organic dyes based on chlorophyll derivatives were synthesized and investigated with respect to applications in dye sensitized solar cells (DSSC). Cyanobacterium Spirulina platensis cultivated on large scales in tropical areas around the Pacific Ocean is an attractive source for production and isolation of pure chlorophyll a. Direct transformation of chlorophyll a into very robust chlorin e6 trimethylester 3 affords an ideal platform for synthesis of dyes for artificial photosynthesis. A series of molecules 24–32 with donor‐π‐acceptor structures and functional groups for immobilization on TiO2 were achieved by subsequent synthetic modifications of 3. Photochemical, theoretical and electrochemical properties of dyes were investigated and their sensitized solar cells performances studied after immobilization on TiO2. [ABSTRACT FROM AUTHOR]

The effectiveness of two liposomal forms of the photosensitizer chlorin E6 differing in their method of preparation was compared. Two types of liposomes were obtained: one containing chlorin E6 in the lipid bilayer; the other, containing the trisodium salt of chlorin E6 in the internal medium. The effectiveness of the prepared liposomes as means for photodynamic therapy (PDT) was studied on L929 mouse fibroblast cell culture. Phototoxicity was estimated upon irradiation with light of wavelength 660 nm and energy density 30 J/cm2. The results showed higher phototoxicity of both liposomal forms of chlorin E6 as compared to the free form of the substance. In turn, liposomes with chlorin E6 included in the lipid bilayer were more phototoxic than liposomes containing the substance in the internal medium. The most probable reason for this phenomenon may be more efficient intracellular accumulation of the active substance for chlorin E6 included in the liposome bilayer. [ABSTRACT FROM AUTHOR]

The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) using photosensitisers is a minimally invasive treatment for malignant tumours. However, ideal photosensitisers are not yet established. Recently, we developed a new photosensitiser, glucose‐conjugated chlorin e6 (G‐Ce6). Objectives: To evaluate the clinical efficacy of vascular‐targeted PDT (VTP), a type of PDT utilising a short drug‐light interval, using G‐Ce6 to treat spontaneously occurring tumours in dogs. Methods: Five dogs with spontaneously occurring tumours (malignant melanoma: three; haemangiopericytoma: two; and squamous cell carcinoma: one) were subjected to VTP. These dogs were intravenously injected with G‐Ce6 at doses of 1–3 mg/kg 5 min before laser irradiation. Tumours were superficially or interstitially irradiated using a 677‐nm diode laser. Results: Repeated VTP decreased tumour size, yielding complete remission in three dogs. Complications such as oedema surrounding normal tissues and fistulae were observed, and the oedema was self‐limiting. The fistula was cured by debriding the necrotic tissues formed after VTP. Conclusions: Our findings demonstrate that VTP using G‐Ce6 had antitumour effects in dogs with spontaneously occurring tumours. [ABSTRACT FROM AUTHOR]

In this study, we have developed pH‐dependent nanogels based on hyaluronic acid (HA) to specifically target acidic tumors. Our initial approach involved modifying HA through the grafting of 3‐(diethylamino)propylamine (DEAP), a molecule known for its responsiveness to changes in pH. This modified HA was termed as HDEA. Subsequently, we performed chemical crosslinking of HDEA using adipic acid dihydrazide (ADH), a crosslinking molecule, resulting in the formation of nanogels referred to as cHDEA. Importantly, the non‐ionized DEAP molecules (with a pKb value of ~pH 7.0) at pH 7.4 support the formation of deswellable cHDEA. This property enables the encapsulation of a photodynamic model drug, chlorin e6 (Ce6), into cHDEA. However, when the DEAP molecules become protonated at pH 6.8, they induce a change in the nanogel structure, causing it to swell due to electrostatic repulsion. As a result, Ce6 is rapidly released from the nanogels. By modulating the pH, we can continuously control the nanogel structure, alternating between swelling and deswelling states. We anticipate that this system offers the advantage of facilitating drug release specifically under acidic tumor conditions while inhibiting drug release under normal pH conditions (i.e., pH 7.4). This approach will serve as an effective strategy for mitigating side effects by efficiently controlling drug release in specific disease areas. [ABSTRACT FROM AUTHOR]

Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity. Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO3 particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method. Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6. Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug's free form. Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a high-risk cancer, and its treatment is an important focus of biomedical research. Immuno-sonodynamic therapy (iSDT), a treatment strategy based on a combination of sonodynamic therapy (SDT) and an immune checkpoint blockade, has been proposed to achieve improved antitumor effects. In this study, chlorin e6 (Ce6) and the PD-1 inhibitor BMS202 were encapsulated into a cell membrane-camouflaged nanoliposome (Bio-Lipo-CB). SDS-PAGE assay and TEM proved the successful wrapping of cell membrane in liposomes, and Bio-Lipo-CB could selectively accumulate in 4T1 cells. Compared with Bio-Lipo-CB alone, Bio-Lipo-CB-SDT showed significant cytotoxicity with abundant ROS production and increased cell apoptosis rate. Moreover, after Bio-Lipo-CB-SDT treatment, calreticulin (CRT) extraversion to the cell membrane, HMGB1 and ATP release to extracellular, indicated immunogenic cell death (ICD). Furthermore, in vivo fluorescence imaging test showed that Bio-Lipo-CB can accumulate in the tumor site after 2 h injection. The in vivo antitumor experiment further confirmed the antitumor efficiency of Bio-Lipo-CB-SDT analysis and demonstrated that Bio-Lipo-CB-SDT induced ICD. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. Our study is a proof of concept of synergistic tumor therapeutics based on SDT and checkpoint blockade immunotherapy using a bionic nanoplatform in TNBC. [ABSTRACT FROM AUTHOR]

Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy (Ce6-PDT), in addition to being the first-line treatment for malignancies, has been shown to lessen skin photoaging, while curcumin is well known for reducing the deleterious effects of ROS. In the current study, PDT with three novel Ce6-curcumin derivatives, a combination of Ce6 and curcumin with various linkers, including propane-1,3-diamine for Ce6-propane-curcumin; hexane-1,6-diamine for Ce6-hexane-curcumin; and 3,3′-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) for Ce6-dipolyethylene glycol (diPEG)-curcumin, were studied for regulation of UVB-induced photoaging on human skin fibroblast (Hs68) and mouse embryonic fibroblast (BALB/c 3T3) cells. We assessed the antiphotoaging effects of Ce6-curcumin derivatives on cell viability, antioxidant activity, the mechanism of matrix metalloproteinase-1 and 2 (MMP-2) expression, and collagen synthesis in UVB-irradiated in vitro models. All three Ce6-curcumin derivatives were found to be non-phototoxic in the neutral red uptake phototoxicity test. We found that Ce6-hexane-curcumin-PDT and Ce6-propane-curcumin-associated PDT exhibited less cytotoxicity in Hs68 and BALB/c 3T3 fibroblast cell lines compared to Ce6-diPEG-curcumin-PDT. Ce6-diPEG-curcumin and Ce6-propane-curcumin-associated PDT showed superior antioxidant activity in Hs68 cell lines. Further, in UVB-irradiated in vitro models, the Ce6-diPEG-curcumin-PDT greatly attenuated the expression levels of MMP-1 and MMP-2 by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and tumor necrosis factor-α (NF-κB) signaling. Moreover, Ce6-diPEG-curcumin effectively inhibited inflammatory molecules, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while accelerating collagen synthesis. These results demonstrate that Ce6-diPEG-curcumin may be a potential therapy for treating skin photoaging. [ABSTRACT FROM AUTHOR]

Water-soluble chlorin e6 cationic derivatives with one and two galactose fragments at the quaternized nitrogen atom were synthesized, and the dark and photoinduced cytotoxicity of the obtained compounds was evaluated. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy. Brain endothelial cell-derived extracellular vesicles are used as biocompatible nanoplatforms to transport mitochondria-targeting photosensitizers into glioblastoma across the blood‒brain barrier. Under light irradiation, the mitochondria-targeting photosensitizers trigger the apoptosis of glioblastoma. [Display omitted] [ABSTRACT FROM AUTHOR]

The problem of oncological diseases has acquired a social and medical character. In this regard, the rapid development of new drugs and methods, as well as modification of existing methods in order to increase their effectiveness, is currently required. The paper aims to develop and study two promising agents for photodynamic therapy. We discussed a new binary complex based on the widely used photosensitizer chlorin E6 with europium, which can solve one of the main disadvantages of drugs for photodynamic therapy: it can be used to treat deeper tumors and act more effectively by transferring luminescence energy between europium and chlorin E6. Our other agent was copper-containing chlorophyllin. Chlorophyllin is a natural component, which is always promising in the development of new drugs. The optical and fluorescent parameters of the agents were determined using physicochemical methods; their ability to generate reactive oxygen species in the presence of two fluorescent probes was studied: 2ʹ, 7ʹ-dichlorodihydrofluorescein and dihydrofluorescein. Thus, we showed the effectiveness of chlorophyllin in comparison with chlorin E6 by 1.92 times at 50 μg / ml E6 and showed the effectiveness of the binary complex even at the minimum concentration of 10 μg / ml. Further research in cell cultures will develop the ways of the possible use of new substances as photosensitizers.

Photothermal therapy (PTT) and sonodynamic therapy (SDT) are becoming promising therapeutic modalities against various tumors in recent years. However, the single therapeutic modality with SDT or PTT makes it difficult to achieve a satisfactory anti-tumor outcome due to their own inherent limitations, such as poor tissue penetration for the near-infrared (NIR) laser and the limited cytotoxic reactive oxygen species (ROS) generated from conventional sonosensitizers irradiated by ultrasound (US). Here, we successfully biosynthesized melanin with a controllable particle size with genetically engineered bacteria harboring a heat-inducible gene circuit. The biosynthetic melanin with 8 nm size and chlorin e6 (Ce6) was further encapsulated into liposomes and obtained SDT/PTT dual-functional liposomes (designated as MC@Lip). The resulting MC@Lip had an approximately 100 nm particle size, with 74.71% ± 0.54% of encapsulation efficiency for melanin and 94.52% ± 0.78% for Ce6. MC@Lip exhibited efficient 1O2 production and photothermal conversion capability upon receiving irradiation by US and NIR laser, producing significantly enhanced anti-tumor efficacy in vitro and in vivo. Especially, US and NIR laser irradiation of tumors received with MC@Lip lead to complete tumor regression in all tested tumor-bearing mice, indicating the great advantage of the combined use of SDT and PTT. More importantly, MC@Lip possessed good photoacoustic (PA) and fluorescence dual-modal imaging performance, making it possible to treat tumors under imaging guidance. Our study provides a novel approach to synthesize a melanin nanoparticle with controllable size and develops a promising combined SDT/PTT strategy to treat tumors. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy of Chlorin e6 (Ce6)-based photodynamic therapy (PDT) for anti-obesity activities in high-fat-diet (HFD)-induced obesity mouse models. We induced obesity in C57BL/6 mice by HFD and administered Ce6 (2.5 or 5 mg/kg) orally with 3 h of incubation. The mice were then exposed to light of high fluence rate (4.96 mW/cm2) or low fluence rate (2.56 mW/cm2) in the designed LED mouse chamber 2–3 days a week for up to 8 weeks. The study also analyzed the pharmacokinetics and optimization of the drug by evaluating the absorption, distribution, metabolism, and excretion (ADME) of Ce6 in the rat models. Both low doses (2.5 mg/kg) and high doses (5 mg/kg) of Ce6 with high irradiation dose showed better anti-obesity effects than other groups with decreased body weight. The lipid accumulation in the liver and adipocyte size in epididymal adipose tissues were found to be decreased by Ce6-PDT in comparison to vehicle-treated HFD groups. We also observed increased levels of the lipidomic biomarkers, such as leptin and LDL cholesterol, while observing decreasing levels of total cholesterol and adiponectin in the Ce6-PDT-treated mice. These findings may provide valuable insight into Ce6-PDT as an alternative and non-invasive therapeutic methodology for obesity and obesity-related diseases. [ABSTRACT FROM AUTHOR]

Novel series of chlorin e6-curcumin derivatives were designed and synthesized. All the synthesized compounds 16, 17, 18, and 19 were tested for their photodynamic treatment (PDT) efficacy against human pancreatic cancer cell lines: AsPC-1, MIA-PaCa-2, and PANC-1. The cellular uptake study was performed in the aforementioned cell lines using fluorescence-activated cell sorting (FACS). 17, among the synthesized compounds with IC50 values of 0.27, 0.42, and 0.21 µM against AsPC-1, MIA PaCa-2, and PANC-1 cell lines, respectively, demonstrated excellent cellular internalization capability and exhibited higher phototoxicity relative to the parent Ce6. The quantitative analyses using Annexin V-PI staining revealed that the 17-PDT-induced apoptosis was dose-dependent. In pancreatic cell lines, 17 reduced the expression of the anti-apoptotic protein, Bcl-2, and increased the pro-apoptotic protein, cytochrome C, which indicates the activation of intrinsic apoptosis, the primary cause of cancer cell death. Structure–activity relationship studies have shown that the incorporation of additional methyl ester moiety and conjugation to the enone moiety of curcumin enhances cellular uptake and PDT efficacy. Moreover, in vivo PDT testing in melanoma mouse models revealed that 17-PDT greatly reduced tumor growth. Therefore, 17 might be an effective photosensitizer for PDT anticancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic information value of chlorin e6 fluorescence visualization of cancer lesion margins in the radical surgical removal of malignant lesions of the external nose. Material and Methods: Thirty patients were examined and underwent surgery for malignant cancer lesions of the external nose at the department for ear, nose and throat cancer during 2017 to 2020. Half of these patients (group 2) received and the rest (group 1) did not receive a preoperative injection of Klein solution and fluorescence visualization of cancer lesion margins. Results: Cancer lesion margins were visualized by fluorescence with chlorin e6 via deep green staining of tumor tissue. The tumor focus appeared violet, and the tumor periphery, crimson when chlorine-e6 fluorescence was excited with 630-633 nm light from a HeNe laser. Because there was no change in tumor lesion margins when compared with visualization without exposing the lesion to laser radiation, exposing the lesion to laser radiation is not mandatory. At three years after surgery, the non-recurrence rate was for 100% for the group of patients who underwent surgery with preoperative injection of Klein solution and fluorescence visualization of cancer lesion margins, and 73.4% for the group of patients who underwent surgery without chlorin e6 fluorescein visualization. Two years after primary surgery, 4 (26.6%) of group 1 patients were diagnosed with recurrent superficial cancer of the skin at the cartilage-bone interface. Conclusion: First, the recurrence rate was 26.6% (4 of 15 patients) for the group of patients who underwent surgery without chlorin e6 fluorescein visualization, which was significantly higher than for the group of patients who underwent surgery with chlorin e6 fluorescein visualization (0 of 15 patients, z = 2.091; р = 0.037). Second, the use of chlorin e6 fluorescein visualization of the margins of a skin lesion of the external nose in patients with malignant tumors of the external nose with tumor spread to the tissues of the medial angle of the eye and eyelid enabled a radical approach to surgical treatment to be employed in 100% of cases.

Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation. Here, using ensemble docking and microsecond molecular dynamics simulations, we identified the two Ce6 binding pockets in HSA, i.e., the Sudlow I site and the heme binding pocket, providing an atomistic description of the binding. Comparing the photophysical and photosensitizing properties of Ce6@HSA with respect to the same properties regarding the free Ce6, it was observed that (i) a red-shift occurred in both the absorption and emission spectra, (ii) a maintaining of the fluorescence quantum yield and an increase of the excited state lifetime was detected, and (iii) a switch from the type II to the type I mechanism in a reactive oxygen species (ROS) production, upon irradiation, took place. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) exhibits characteristics such as hypoxia, weak acidity, and enrichment of glutathione and hydrogen peroxide (H 2 O 2), which greatly limits the effectiveness of tumor magnetic resonance imaging (MRI) and photodynamic therapy (PDT). Carbon dots (CDs) nanozymes are excellent candidate materials with both diagnostic and therapeutic potential. However, CDs nanozymes with both ultra-high relaxation rate and good therapeutic effect are still to be developed. Herein, novel carbon dots (MPC-CDs) were synthesized from polyethyleneimine (PEI), the photosensitizer hexahydroporphyrin (Ce6) and manganese. The Ce6 enabled the MPC-CDs to exhibit excellent PDT therapeutic ability, with a singlet oxygen yield as high as 1.52. The doping of the metal manganese gave the complexes CAT-like activity, and the singlet oxygen rate was further increased in the presence of H 2 O 2 , up to 1.97. In addition, manganese endowed the CDs with better MRI capabilities, and the r 1 and r 2 relaxation rates were significantly improved by 7.8-fold and 4.6-fold under acidic and H 2 O 2 conditions. The in vitro and in vivo results showed that MPC-CDs could achieve TME-responsive MR imaging and synergistic anti-tumor effects, providing an effective strategy to further enhance the effectiveness of tumor diagnosis and treatment. [Display omitted] • Manganese doped Ce6 nanodots (MPC-CDs) increased relaxation rates of 780 % and 460 % for r 1 and r 2 upon tumor microenvironment responsiveness. • Mn increased CAT-like activity of MPC-CDs, and the singlet oxygen rate was further increased in the presence of H 2 O 2 , up to 1.97. [ABSTRACT FROM AUTHOR]

ABSTRACT Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock proteins (HSPs), which enhances bacterial resistance. Herein, we incorporated HSP inhibitors with PDT to evaluate the effect on Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis under planktonic conditions and on cariogenic biofilms. Additionally, a model of caries was established in 2-week-old rats, and anticaries properties were evaluated by Keyes’ scoring. Importantly, the combination of HSP inhibitors and PDT had outstanding efficiency in inhibiting the growth of tested Streptococcus strains and the formation of either monomicrobial or multispecies biofilms in vitro. In addition, the quantity of colonized streptococci and the severity of carious lesions were also distinctly suppressed in vivo. Overall, the synergistic application of HSP inhibitors and PDT has promising potential in the prevention and treatment of dental caries. IMPORTANCE Effective therapies for the prevention and control of caries are urgently needed. Cariogenic streptococci play a key role in the occurrence and progression of caries. Recently, photodynamic therapy has been demonstrated to have good antibacterial efficiency, but it can cause a heat shock response in bacteria, which may weaken its practical effects. We indicate here an effective therapeutic strategy of combining heat shock protein inhibitors and photodynamic therapy, which shows excellent inhibition toward three dominant streptococci related to caries and suppression of carious progression in a rat model. Further development for clinical application is promising.

Photodynamic therapy (PDT) can eradicate not only cancer cells but also stimulate an antitumor immune response. Herein, we describe two efficient synthetic methodologies for the preparation of Chlorin e6 (Ce6) from Spirulina platensis and address the phototoxic effect of Ce6 in vitro along with antitumor activity in vivo. Melanoma B16F10 cells were seeded and phototoxicity was monitored by the MTT assay. The C57BL/6 mice were subcutaneously inoculated on the left and right flank with B16F10 cells. The mice were intravenously injected with Ce6 of 2.5 mg/kg and then exposed to red light (660 nm) on the left flank tumors 3 h after the injection. The immune response was studied by analyzing Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and Interleukin-2 (IL-2) of the right flank tumors through qPCR. Our results revealed that the tumor was suppressed not only in the left flank but also in the right flank, where no PDT was given. The upregulated gene and protein expression of IFN-γ, TNF-α, and IL-2 revealed antitumor immunity due to Ce6-PDT. The findings of this study suggest an efficient methodology of Ce6 preparation and the efficacy of Ce6-PDT as a promising antitumor immune response. [ABSTRACT FROM AUTHOR]

A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide a (chlorin e6 derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes—liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5–2 times that of the reference dye chlorin e6 trisodium salt—one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and N-vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles. [ABSTRACT FROM AUTHOR]

The fluorescence anisotropy of photosensitizers Radachlorin and chlorin e6 was studied using the time-resolved single photon-counting technique under one- and two-photon excitation within the Soret absorption band. A very small negative anisotropy was observed in both photosensitizers under one-photon excitation in the vicinity of the absorption maximum within the wavelength range of 395–405 nm. Meanwhile, two-photon excitation of the photosensitizers in the same spectral range demonstrated high fluorescence anisotropy with the maximum value of about 0.43. The drastic difference of the fluorescence anisotropy parameters at one- and two-photon excitation modes was suggested to be due to the different symmetries of one- and two-photon absorption tensors when two-photon absorption tensor components have comparable values. The variation of excitation wavelengths in the spectral range of 375–425 nm demonstrated nonlinear wavelength dependence of anisotropy of both Radachlorin and chlorin e6, with opposite tendencies at one- and two-photon excitation. The data obtained suggest that one-photon excitation at about 405 nm often utilized in FLIM experiments is not sensitive to fluorescence anisotropy in Radachlorin and chlorin e6 and therefore cannot be used for the determination of anisotropy/rotational diffusion time in these molecules. Meanwhile, two-photon excitation can provide high fluorescence anisotropy and accurate determination of the rotational diffusion time. At the same time, one-photon excitation at about 405 nm can be used for the accurate evaluation of fluorescence lifetimes within the standard FLIM schematic where fluorescence polarization is not taken into account. [ABSTRACT FROM AUTHOR]

[Display omitted] This study was conducted to construct a multifunctional nanodrug delivery system (NDDS) to deplete glutathione (GSH) in tumor cells and amplify oxidative stress, enhancing the synergistic effect of chemotherapy and photodynamic therapy (PDT). l -Buthionine-sulfoximine (BSO) and chlorin e6 (Ce6) were loaded into mesoporous silicon nanoparticles (MSN), and then MSN were modified with oxidized hyaluronic acid (OHA) as a pore-blocking agent. Cisplatin (Pt(II)) was further loaded by a coordination reaction with carboxyl groups in OHA to yield a multifunctional NDDS (denoted as MSN@OHA-Ce6/BSO/Pt). The physicochemical properties and antitumor activity of the prepared nanoparticles were characterized in detail. In vitro and in vivo experiments demonstrated that OHA was shed from MSN@OHA-Ce6/BSO/Pt under acidic conditions in tumors, resulting in the release of free BSO, Ce6, and Pt(II). The released BSO could reduce intracellular GSH expression by 48.8 %, effectively enhancing the PDT effect of Ce6 and the chemotherapy effect of Pt(II). Finally, the tumor inhibitory rate (vs saline) reached 73.8 % ± 2.5 % for MSN@OHA-Ce6/BSO/Pt in A549/DDP tumor-bearing nude mice. Therefore, the multifunctional NDDS significantly enhanced the synergistic effect of PDT and chemotherapy. [ABSTRACT FROM AUTHOR]

Aim: To develop a new drug delivery system (DDS) that can load chemotherapy agents and photosensitizer chlorin e6 (Ce6) onto the pores and surfaces of mesoporous silica nanoparticle (MSN) separately., Methods: Doxorubicin (DOX) was loaded into the pores of MSNs. Then, polyethyleneimine (PEI) was used to coat the surface of MSN to protect DOX, and then manganese dioxide (MnO 2 ) nanoparticles were loaded through adding potassium permanganate (KMnO 4 ) to bind with Ce6. Finally, polydopamine (PDA) was coated and coupled with hyaluronic acid (HA)., Results: The synthesized versatile nanoparticle was pH-sensitive and exhibited positive photodynamic therapy (PDT) performance. Besides, it could be observed that the nanoparticles were efficiently taken up by tumor cells through confocal laser scanning microscopy (CLSM) and flow cytometry. Additionally, in vitro experiments suggested that the nanoparticles had pleasing toxicity to various tumor cells and equally positive therapeutic effect when curcumin replaced DOX., Conclusion: Our work suggests that the nanoparticles designed by our strategy have satisfactory combination therapy performance and can enable more chemotherapy drugs to be used in photodynamic-chemo combination therapy.