Photodynamic Agents Research Articles

Synergistic antibiosis with spatiotemporal controllability based on multiple-responsive hydrogel for infectious cutaneous wound healing

Bacterial infection is one of serious problems hindering tissue regeneration, but strategies able to perform proper antibiosis with spatiotemporal controllability to manipulate the local inflammation and immunity for effective healing of infected wound is still a challenge. Herein, we fabricated a smart hydrogel (CNMs@HA-PDA-PL) with multiple responsiveness to near infrared radiation, visible light, hyaluronidase and hydrogen peroxide for promoted healing of the infected wound via controllable anti-bacteria at designed locations and time periods as well as the on-demand regulation of local inflammation and immunity. The hydrogel consists of hyaluronic acid (HA) modified graphitic carbon nitride (g-C3N4) microsphere (CNMs), antimicrobial peptides (ε-Poly-l-lysine, ε-PL) and polydopamine (PDA). The PDA framework and CNMs respectively serve as photothermal agent and photodynamic agent to generate heat and radical for instant damage of major bacteria on/surrounding the hydrogel, while the ε-PL is in charge of the sustained antibiosis in long term to eliminate the deep bacteria away from the hydrogel via biochemical process. Once the hydrogel was located at infected area, the over-expressed hyaluronidase and hydrogen peroxide would sequentially spread CNMs and ε-PL to start photodynamic therapy and biochemical therapy in designed range after initial photothermal therapy, resulting in synergistic antibiosis with spatiotemporal controllability. This stepwise anti-bacteria process meanwhile manipulated the local inflammatory microenvironment to promote tissue regeneration, in which the hydrogel gradually performed effective recruitment of inflammatory (M1) macrophages and continuous phenotypic transition of these M1 macrophages toward pro-reparative (M2) macrophages, leading to a rapid healing of the infectious cutaneous wound.

Novel benzoylthiourea derivatives had differential anti-inflammatory photodynamic therapy potentials on in vitro stimulated mammalian macrophages

Novel benzoylthioureas, N-((5-chloropyridin-2yl)carbamothioyl)benzamide, (HL1), N-((2-chloropyridin-3yl)carbamothioyl)benzamide, (HL2), N-((5-bromopyridin-2yl)carbamothioyl)benzamide, (HL3) and N-(Naphthalene-1-yl(phenyl)carbamothioyl)benzamide, (HL4), were synthesized. Their characterizations were made by FT-IR,1H NMR and 13C NMR spectrophotometric analysis. Single crystal X-ray diffraction measurements were conducted to determine the crystal structure of HL1 and HL4. The HL1 crystallization conditions are: in the monoclinic crystal system with P21/c space group, Z = 2, a = 8.118(2) Å, b = 12.056(3) Å, c = 13.753(4) Å. HL4crystallization conditions are: in the orthorhombic crystal system with Pbca space group, Z = 8, a = 19.597(9) Å, b = 8.270(4) Å, c = 24.299(11) Å. Investigation of photodynamic and antiinflamatory effects of these compounds revealed that they are potent adducts. Using these derivatives, mammalian macrophages were stimulated with LPS to test their anti-inflammatory activity. Based on pro-inflammatory cytokine production levels, the photodynamic anti-inflammatory activity of these adducts were found to differ. Our results showedthat benzoylthioureas can be used as potential photodynamic therapy agents to suppress the excessive inflammatory reactions encountered in autoimmune and inflammatory disorders.

Polylactide nanoparticles encapsulating indocyanine green for photothermal therapy of prostate cancer cells

BackgroundThe aim of this study is to investigate the in vitro phototherapeutic potential of indocyanine green (ICG) loaded polylactide (PLA) nanoparticles on prostate cancer cells. Many attempts at designing drug delivery systems against cancer were made that incorporates ICG as a photothermal, photodynamic or imaging agent. However, most of these systems contain at least one more drug, making it hard to assess the effects of ICG alone. MethodsNanoparticles (ICGNP) were prepared via nanoprecipitation. The effects of phase volume ratio and ICG concentration on size, loading capacity and encapsulation efficiency were explored. Photothermal and photodynamic properties of ICGNP were examined. PC-3 cells were used for cell viability tests. Irradiation was achieved via custom built 809-nm computer controlled diode laser at 1 W/cm2 (up to 600 J/cm2). Data were analyzed by ANOVA followed by Tukey's test (p ≤ 0.05). ResultsICGNP exhibited mean size of 300 nm with low polydispersity, and zeta potential of -14 mV. Upon laser irradiation, ICGNP were capable of causing temperature increase and producing singlet oxygen. On PC-3 cells, ICGNP were proved to be as effective as free ICG in inducing cell death. The measured temperature increase in culture medium and experiments with singlet oxygen quenchers suggest that the decrease in cell viability was mainly the result of photothermal action. ConclusionsICGNP was effective as a photothermal agent on PC-3 cells but further improvements are required to increase ICG loading capacity for it to be useful on a wide range of cell types.

Graphene Oxide-Gold Nanorods Nanocomposite-Porphyrin Conjugate as Promising Tool for Cancer Phototherapy Performance.

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy.

Direct [4 + 2] Cycloaddition to Isoquinoline-Fused Porphyrins for Near-Infrared Photodynamic Anticancer Agents.

The synthesis of efficient porphyrin-based photosensitizers with intense near-infrared (NIR) absorption is in high demand for photodynamic therapy (PDT) but remains a challenging task. Herein we show the construction of a type of isoquinoline-fused porphyrins 3 and 4 with an impressive NIR-absorbing capacity. In light of the extraordinary singlet oxygen generation capabilities of 3 upon NIR irradiation, the representative nanoparticles (3a-NPs) assembled show excellent tumoricidal behavior with good biocompatibility in the phototherapeutic window (650-850 nm).

Alkylverdazyls as a Source of Alkyl Radicals for Light-Triggered Cancer Cell Death.

Two alkylated verdazyl radicals (AlkVZs) were investigated as active compounds for photoinitiated controlled MCF-7 cell death. Observed results unambiguously showed that AlkVZ could be a potential structural moiety for the design of a novel family of photodynamic therapy agents. The main advantage of the proposed substances is an oxygen-independent generation of active radicals, which play a pivotal role in the treatment of oxygen-deficient tumors.

Multifunctional Photoactive Hydrogels for Wound Healing Acceleration.

Light is an attractive tool that has a profound impact on modern medicine. Particularly, light-based photothermal therapy (PTT) and photodynamic therapy (PDT) show great application prospects in the prevention of wound infection and promoting wound healing. In addition, hydrogels have shown attractive advantages in the field of wound dressings due to their excellent biochemical effects. Therefore, multifunctional photoresponsive hydrogels (MPRHs) that integrate the advantages of light and hydrogels are increasingly used in biomedicine, especially in the field of wound repair. However, a comprehensive review of MPRHs for wound regeneration is still lacking. This review first focuses on various types of MPRHs prepared by diverse photosensitizers, photothermal agents (PHTAs) including transition metal sulfide/oxides nanomaterials, metal nanostructure-based PHTAs, carbon-based PHTAs, conjugated polymer or complex-based PHTAs, and/or photodynamic agents (PHDAs) such as ZnO-based, black-phosphorus-based, TiO2-based, and small organic molecule-based PHDAs. We also then discuss how PTT, PDT, and photothermal/photodynamic synergistic therapy can modulate the microenvironments of bacteria to inhibit infection. Overall, multifunctional hydrogels with both therapeutic and tissue regeneration capabilities have been discussed and existing challenges, as well as future research directions in the field of MPRHs and their application in wound management are argued.

COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents.

Photodynamic therapy (PDT) for cancer treatment has drawn increased attention over the last decades. Herein, we introduce a novel family of low-molecular-weight coumarins as potential PDT anticancer tools. Through a systematic study with a library of 15 compounds, we have established a detailed structure–activity relationship rationale, which allowed the selection of three lead compounds exhibiting effective in vitro anticancer activities upon visible-light irradiation in both normoxia and hypoxia (phototherapeutic indexes up to 71) and minimal toxicity toward normal cells. Acting as excellent theranostic agents targeting mitochondria, the mechanism of action of the photosensitizers has been investigated in detail in HeLa cells. The generation of cytotoxic reactive oxygen species, which has been found to be a major contributor of the coumarins’ phototoxicity, and the induction of apoptosis and/or autophagy have been identified as the cell death modes triggered after irradiation with low doses of visible light.

Ultrathin tellurium nanosheets for simultaneous cancer thermo-chemotherapy

The emerging two-dimensional monoelemental materials (2D Xenes) have been commonly supposed as promising drug delivery carriers, photothermal and photodynamic therapeutic agents, biosensors, theranostics, and some other candidates for biomedical applications. Here, high-performance and bioactive ultrathin 2D Tellurium nanosheets (Te NSs) are prepared by a simple but efficient liquid-phase exfoliation approach. The as-obtained Te NSs possess a mean size of ∼90 nm and a mean thickness of ∼5.43 nm. The pegylation Te NSs (Te-PEG NSs) possess excellent biocompatibility and stability. The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55% under 808 nm laser irradiation. Additionally, Te-PEG NSs exhibit an extremely high loading capacity of chemo drug (∼162%) owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority. The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy, comparing to any other single therapeutic modalities. Therefore, our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine.

Effect of solution pH on as-synthesized and calcined WO3 nanoparticles synthesized using sol-gel method

Tungsten oxide nanoparticles are particularly suitable for a wide range of applications like non-invasive cancer treatment, water treatment, gas sensing, and so on. In this paper, the effect of the solution pH on as-synthesized WO 3 nanoparticles and calcined WO 3 nanostructures at 500 °C is investigated to achieve appropriate WO 3 nanoparticles with a simple and low-price sol-gel method. The results declare that solution pH significantly affects the morphology, crystallinity, chemical bonds, and optical properties of WO 3 nanoparticles. Increasing solution pH from 1 to 2 with the step of 0.5 leads to crystal phase transition and increment of the hexagonal phase percentage. The size of nanoparticles increases with increasing the solution pH in as-synthesized. So, it turns out that solution pH affects the particles growth process. In addition, the results reveal that increasing the solution pH leads to a blue shift at the optical absorption edges. Also, the indirect energy bandgap of WO 3 particles increases/decreases with increasing pH in the case of as-synthesized/calcined samples. The energy bandgaps of calcined samples were generally lower than as-synthesized ones. The sample prepared at pH = 1 shows the highest absorption (about ten times higher than other samples at λ = 300 nm) and low reflection in the whole range of the spectrum that makes it a worthy candidate for photocatalysis applications. • Synthesis of WO 3 NPs by simple and low-price sol-gel method. • WO 3 NPs as excellent photocatalysis and photodynamic agent. • Study the effects of the solution pH on as-synthesized and calcined WO 3 NPs. • Significant effect of pH on structural and optical properties of WO 3 NPs. • Producing of high absorption/low reflection WO 3 NPs for photocatalysis application.

Mimetic sea cucumber-shaped nanoscale metal-organic frameworks composite for enhanced photodynamic therapy

Therapeutic resistance caused by hypoxia tumor microenvironment (TME) is one of the main challenges for the development of nanoscale delivery systems, particular for the photodynamic agents. In this work, porphyrin-based metal-organic frameworks composite ACF@PCN-222@MnO2-PEG (APM) with the mimetic sea cucumber morphology was post-synthesized for using in photodynamic therapy (PDT) against hypoxia. Besides the good colloidal stability, as-synthesized APM nanoparticles also exhibited the well biocompatibility and H2O2-triggered drug releasing. After being reacted with endogenous H2O2, the amorphous MnO2 layer on the APM outersurface could quickly decompose to produce abundant oxygen, self-compensating for the consumption of photodynamic process. Meanwhile, the highly loaded hypoxia inhibitors acriflavine (ACF) of 18.7 wt% in APM was released to down-regulate the expression level of hypoxia-inducible factors (HIF). Combining with the self-generating oxygen and ACF inhibitors, the tumor hypoxia could be greatly relieved and the better tumor suppression effect by PDT have been demonstrated in vivo. This self-suppling oxygen nanosystem triggered by endogenous tumor markers proves a feasible way for remodeling the hypoxia TME and to achieve better therapeutic performances.

A new porphyrin as selective substrate-based inhibitor of breast cancer resistance protein (BCRP/ABCG2)

The ABCG2 transporter plays a pivotal role in multidrug resistance, however, no clinical trial using specific ABCG2 inhibitors have been successful. Although ABC transporters actively extrude a wide variety of substrates, photodynamic therapeutic agents with porphyrinic scaffolds are exclusively transported by ABCG2. In this work, we describe for the first time a porphyrin derivative (4B) inhibitor of ABCG2 and capable to overcome multidrug resistance in vitro. The inhibition was time-dependent and 4B was not itself transported by ABCG2. Independently of the substrate, the porphyrin 4B showed an IC50 value of 1.6 μM and a mixed type of inhibition. This compound inhibited the ATPase activity and increased the binding of the conformational-sensitive antibody 5D3. A thermostability assay confirmed allosteric protein changes triggered by the porphyrin. Long-timescale molecular dynamics simulations revealed a different behavior between the ABCG2 porphyrinic substrate pheophorbide a and the porphyrin 4B. Pheophorbide a was able to bind in three different protein sites but 4B showed one binding conformation with a strong ionic interaction with GLU446. The inhibition was selective toward ABCG2, since no inhibition was observed for P-glycoprotein and MRP1. Finally, this compound successfully chemosensitized cells that overexpress ABCG2. These findings reinforce that substrates may be a privileged source of chemical scaffolds for identification of new inhibitors of multidrug resistance-linked ABC transporters.

Synthesis and photodynamic effect of 3-substituted methyl pyropheophorbide-a derivatives as novel photodynamic therapeutic agents for cancer treatment

The unique ability of chlorophyll derivatives to accumulate in tumor tissues and cause a photodynamic effect under laser radiation has been successfully used in photodynamic therapy (PDT). Previous research on modified peripheral substituents in chlorophyll showed that the presence and position of substituents in chlorin derivatives remarkably affect biological activities. Herein, we synthesized methyl pyropheophorbide-a (MPPa) derivatives, which are chlorophyll-a derivatives with heterocyclic aromatic substituents or pyrazole moieties on the peripheral positions. Then, we examined the PDT effects of these new derivatives in vitro and in vivo.

Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro.

Simple SummaryPhotodynamic priming is an emerging strategy that leverages subtherapeutic photochemistry for therapeutic benefits, often used as part of combination regimens. Our study aimed to couple photodynamically priming with antagonism of the prostaglandin E receptor 4, a therapeutic target linked to cancer-associated migration, invasion, angiogenesis, and immune evasion. Photodynamic priming and antagonism of the prostaglandin E receptor 4 independently attenuated OVCAR-5 ovarian cancer cell migration in a gap closure model, though their combination induced the most significant reductions. More potent combination effects were revealed when invasiveness was characterized using a transwell invasion model with CAOV3 ovarian cancer cells. Immunoblotting identified the epithelial growth factor receptor, cAMP-response element binding protein, and extracellular signal-regulated kinase 1/2 as potential mediators of these combinational effects. This work provides new evidence of a novel and clinically relevant combination strategy to address metastatic behavior, a major challenge in the treatment of cancer.The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E2 receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists.

Fabrication of nanohybrids toward improving therapeutic potential of a NIR photo-sensitizer: An optical spectroscopic and computational study

Implementation of near infrared radiation (NIR) active drugs in photodynamic therapy (PDT) is considered as a highly promising tool in therapeutic application. Because of its strong NIR absorbance, indocyanine green (ICG) has become an attractive choice in emerging photo-theranostics. ICG generates singlet oxygen as well as shows photothermal effect under NIR irradiation. However, ICG is unable to produce sufficient amount of others types of reactive oxygen species (ROS) such as superoxide, hydroxyl radical. But, its ability of singlet oxygen generation under NIR irradiation is arrested by its tendency to aggregate in aqueous medium. Because of this limitation, it shows better effectiveness in photothermal therapy compare to it’s action as a photodynamic agent. Herein, we have addressed to overcome this limitation via the fabrication of zinc oxide (ZnO) based ICG-ZnO nanohybrid which provides lesser H-aggregation between ICG molecules on its surface and yield significantly greater amount of ROS relative to ICG upon photoexcitation, due to excited state electron transfer from ICG to ZnO. Also, this surface functionalization prevents aggregation of ICG in water significantly. Classical MD simulation shows the dimeric structure of ICG breakes down on ZnO surface which corroborates results from the aggregation study in water. Density functional theory (DFT) along with time-dependent DFT studies elucidate that upon photoexcitation electron transfer takes place from the higher energy orbital of ICG to the conduction band of ZnO. The greater efficiency in ROS generation by the ICG-ZnO nanohybrid than ICG or ZnO demonstrates remarkable antimicrobial activity against gram-negative bacteria E. coli. Overall, the present study highlights the scope of developing ICG-ZnO nanohybrid as a highly efficient NIR agent for use in antibacterial photodynamic therapy.

Cyanoarylporphyrazines with High Viscosity Sensitivity: A Step towards Dosimetry-Assisted Photodynamic Cancer Treatment.

Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an “ideal photosensitizer” and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. Pz II and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.

Orange Trunk Waste-Based Lignin Nanoparticles Encapsulating Curcumin as a Photodynamic Therapy Agent against Liver Cancer

Orange wood biomass is an interesting lignocellulosic material, but its lignin has been little explored. As a structural macromolecule present in the plant cell wall, lignin has been used in nanoencapsulation and nanomedicine, standing out as a good drug carrier. In this study, lignin was extracted by soda pulping process and used to produce nanoparticles for curcumin encapsulation and subsequent application in photodynamic therapy (PDT). The nanoparticles were synthesized by the solvent shifting process and characterized with UV–vis, fluorescence, dynamic light scattering (DLS), ζ-potential, and scanning electron microscopy (SEM). The lignin was soluble in organic solvent and presented an extraction yield of 20.6 ± 2%. The Fourier transform infrared (FTIR) spectroscopy and NMR signals showed that the lignin presents hardwood-type characteristics. The lignin nanoparticles were easily obtained and presented average sizes of 284 ± 60, 287 ± 60, and 502 ± 100 nm for pure lignin, 1% curcumin, and 5% curcumin nanoparticles, respectively. They exhibited a negative ζ-potential of about −42 ± 5 mV. The formulations were evaluated for 30 days and remained stable in phosphate-buffered saline (PBS). The curcumin encapsulation yields were high, above 90% in all formulations. Scanning electron microscopy (SEM) images showed that the nanoparticles are spherical and homogeneous. Studies using hepatocarcinoma (HTC) and HepaRG cells showed that the lignin nanoparticles were nontoxic within 4 h of incubation, and for nanoparticles containing 5% curcumin, toxicity was observed upon application of light in PDT experiments.

Lactose-conjugated porphyrin: synthesis and photobiological evaluation as potential agents for photodynamic therapy

Porphyrin-based photosensitizers are conventional photodynamic agents that are used clinically. However, their clinical applications have been overshadowed by poor water solubility. In addition, they have weak tumor selectivity, which may cause undesirable side effects. The preparation of novel porphyrin derivatives has been explored for potential applications in photodynamic therapy (PDT). To achieve this goal, lactose-conjugated porphyrin nanoparticles (Lac-Por NPs) have been synthesized and characterized. PDT with Lac-Por NPs exhibited tumor-specific cytotoxicity in lactose receptor-overexpressing HepG2 cells in vitro and in vivo. In summary, we designed and synthesized lactose conjugate porphyrins with enhanced water solubility and tumor selectivity. This work expands the application range of porphyrin-based photosensitizers for cancer treatment.

OS06.5A Fluorescence image-guided resection of intracranial meningioma: an experimental in vivo study on nude mice

Abstract BACKGROUND The use of photodynamic agents in malignant cranial tumor surgery is quite common. For example five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Until today there is no comparable selective fluorescent substance available for meningiomas. Nevertheless, there is a demand for intraoperative fluorescent identification of e.g. invasive skull base meningiomas to increase radicality. This study was established to investigate fluorescent image-guided resection with somatostatin receptor labelled fluorescence dye for intracranial meningioma in the nude mice. MATERIAL AND METHODS Primary meningioma cell culture samples were stereotactically implanted subdural into 20 nude mice. 90 days after inoculation of the cells, a cranial MRI with contrast agent revealed tumor growth. After detection of tumor mass in MRI, FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide was injected intravenously and tumor mass was hereafter resected under visualization via fluorescence microscope and endoscope. After attempted total resection, animal were sacrificed brain slices were obtained and histologically analysed to verify the resection extent. RESULTS In 18 mice tumor growth was detected in MRI after 90 days of inoculation. The tumor mass could be clearly identified with fluorescence microscope and endoscope after injecting FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide. The tumor margins could be better visualized. After fluorescence-guided resection no remaining tumor could be identified in histological analysis. CONCLUSION This study describes for the first time the use of FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide and demonstrates its value of fluorescent identification of meningioma cells in vivo. Furthermore, the authors established a new experimental animal model for fluorescence meningioma surgery.

BODIPY‐Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen

AbstractDeveloping Type‐I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type‐I process. Herein, we report a series of α,β‐linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2−.) by the Type‐I process upon light irradiation. The triplet formation originates from an effective excited‐state relaxation from the initially populated singlet (S1) to triplet (T1) states via an intermediate triplet (T2) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2−. by inter‐molecular charge transfer to molecular oxygen. The energy gap of T1‐S0 is smaller than that between 3O2 and 1O2 thereby precluding the generation of singlet oxygen by the Type‐II process. The trimer exhibits superior PDT performance under the hypoxic environment.