Singlet Oxygen Generation Capability Research Articles

Molecular Design of Highly Efficient Heavy‐Atom‐Free Triplet BODIPY Derivatives for Photodynamic Therapy and Bioimaging

AbstractNovel BODIPY photosensitizers were developed for imaging‐guided photodynamic therapy. The introduction of a strong electron donor to the BODIPY core through a phenyl linker combined with the twisted arrangement between the donor and the BODIPY acceptor is essential for reducing the energy gap between the lowest singlet excited state and the lowest triplet state (ΔEST), leading to a significant enhancement in the intersystem crossing (ISC) of the BODIPYs. Remarkably, the BDP‐5 with the smallest ΔEST (ca. 0.44 eV) exhibited excellent singlet oxygen generation capabilities in both organic and aqueous solutions. BDP‐5 also displayed bright emission in the far‐red/near‐infrared region in the condensed states. More importantly, both in vitro and in vivo studies demonstrated that BDP‐5 NPs displayed a high potential for photodynamic cancer therapy and bioimaging.

Molecular Design of Highly Efficient Heavy-Atom-Free Triplet BODIPY Derivatives for Photodynamic Therapy and Bioimaging.

Novel BODIPY photosensitizers were developed for imaging-guided photodynamic therapy. The introduction of a strong electron donor to the BODIPY core through a phenyl linker combined with the twisted arrangement between the donor and the BODIPY acceptor is essential for reducing the energy gap between the lowest singlet excited state and the lowest triplet state (ΔEST ), leading to a significant enhancement in the intersystem crossing (ISC) of the BODIPYs. Remarkably, the BDP-5 with the smallest ΔEST (ca. 0.44 eV) exhibited excellent singlet oxygen generation capabilities in both organic and aqueous solutions. BDP-5 also displayed bright emission in the far-red/near-infrared region in the condensed states. More importantly, both in vitro and in vivo studies demonstrated that BDP-5 NPs displayed a high potential for photodynamic cancer therapy and bioimaging.

High antimicrobial photodynamic activity of photosensitizer encapsulated dual-functional metallocatanionic vesicles against drug-resistant bacteria S. aureus.

Developments in the field of photodynamic therapy (PDT) are being made by investigating appropriate photosensitizers (PSs) and enhancing the penetration effect of light by developing new nano-carriers. So, to boost the PDT effect, in the present work, new metallocatanionic vesicles were fabricated by a convenient, efficient, green and inexpensive method to encapsulate PSs and evaluate their antimicrobial PDT against the drug-resistant bacterium Staphylococcus aureus. They were prepared from a combination of a double-chained copper-based cationic metallosurfactant (CuCPCII) and an anionic surfactant sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol OT or AOT). The surface charge, structure and ability to encapsulate oppositely charged photosensitizers are some crucial factors that need to be controlled for their effective utilization in PDT. In this approach, two of the fractions, one each from a cationic rich and anionic rich side, were selected to encapsulate cationic (methylene blue; MB) and anionic (rose bengal (RB)) PSs after characterization by SAXS, AFM, FESEM, DLS, and zeta-potential, and conductivity measurements. Afterwards, PDT was performed on S. aureus (a multidrug-resistant bacterium) by the colony forming unit (CFU) method using PS encapsulated metallocatanionic vesicles that demonstrated high bactericidal activity by using visible light (532 nm) and facilitated the generation of singlet oxygen. The singlet oxygen generation capability of both the PSs was enhanced under irradiation when encapsulated in metallocatanionic vesicles because the presence of metal accelerated the intersystem crossing of triplet oxygen to singlet oxygen. Furthermore, these studies reveal that the metallocatanionic vesicles have dual functionality i.e. encapsulate PSs and even show dark toxicity against S. aureus. To study the killing of S. aureus, bacterial DNA was extracted and its interactions and conformational changes in the presence of metallocatanionic vesicles were analyzed via., UV-Visible, and circular dichroism (CD) spectroscopy. Comet assay (single-cell gel-electrophoresis) demonstrated the DNA damage after PDT treatment in an individual cell. The bacterial DNA damage was more with the metallosurfactant rich 70 : 30 fraction than with the 30 : 70 fraction, in combination with RB under irradiation. This work provides a new metal hybrid smart material that possesses dual functionality and is prepared by an easy, economical and feasible procedure which resulted in enhanced PDT against a drug-resistant bacterium, thus, providing an alternative for antibacterial therapy.

Fluorine-substituted tetracationic ABAB-phthalocyanines for efficient photodynamic inactivation of Gram-positive and Gram-negative bacteria

Herein, we report the synthesis and characterization of new amphiphilic phthalocyanines (Pcs), the study of their singlet oxygen generation capabilities, and biological assays to determine their potential as photosensitizers for photodynamic inactivation of bacteria. In particular, Pcs with an ABAB geometry (where A and B refer to differently substituted isoindole constituents) have been synthesized. These molecules are endowed with bulky bis(trifluoromethylphenyl) groups in two facing isoindoles, which hinder aggregation and favour singlet oxygen generation, and pyridinium or alkylammonium moieties in the other two isoindoles. In particular, two water-soluble Pc derivatives (PS-1 and PS-2) have proved to be efficient in the photoinactivation of S. aureus and E. coli, selected as models of Gram-positive and Gram-negative bacteria.

Self-assembled nanostructured photosensitizer with aggregation-induced emission for enhanced photodynamic anticancer therapy

Three nanostructured photosensitizers with aggregation-induced emission (AIE) characteristics based on 2,3-bis(4ʹ-(diphenylamino)-[1,1ʹ-biphenyl]-4-yl) fumaronitrile (BDBF) were prepared for image-guided photodynamic therapy (PDT). BDBF was encapsulated with Pluronic F-127 (F127) to form usual spherical nanoparticles (F127@BDBF NPs) with a red fluorescence emission and 9.8% fluorescence quantum yield (FQY). Moreover, BDBF self-assembled into nanorods (BDBF NRs) in water. Compared with F127@BDBF NPs, BDBF NRs exhibited stronger orange fluorescence with a higher FQY of 23.3% and similar singlet oxygen (1O2) generation capability. BDBF NRs were further modified with F127 to form BDBF@F127 NRs with the same 1O2 generation ability as BDBF NRs. The three nanostructures exhibited a higher 1O2 production capacity than BDBF molecule in dissolved state and favorable stability in an aqueous solution as well as under physiological condition. In vitro photocytotoxicity experiments indicated that the three nanostructures inhibited tumor cell proliferation effectively. Therefore, to construct eligible nanostructures with a high FQY and 1O2 generation ability, simple self-assembly can serve as a valuable method to prepare photosensitizers with enhanced PDT.

Rapid Synthesis of γ-Halide/Pseudohalide-Substituted Cyanine Sensors with Programmed Generation of Singlet Oxygen.

A range of γ-halide/pseudohalide-substituted cyanine-based photosensitizers with programmed levels of singlet oxygen generation capability have been developed as theranostic agents for photodynamic therapy of cancer and infectious diseases.

A comparative study of the singlet oxygen generation capability of a zinc phthalocyanine linked to graphene quantum dots through π-π stacking and covalent conjugation when embedded in asymmetric polymer membranes

Following the establishment of graphene quantum dots as potential phthalocyanine supports in photoactive membrane preparation for phthalocyanines lacking linkage functional groups, the practical efficiency of π-π stacking versus covalent linkage was investigated. Synthesized materials were characterized using FT-IR, Raman, powder X-ray diffraction, and UV–Vis spectroscopies and also by transmission electron and scanning electron microscopies. Phthalocyanine loadings onto graphene quantum dots of 0.40 mg/mg and 0.14 mg/mg (Pc mass/conjugate mass) for the π-π stacked and covalent linked conjugates respectively were observed. Covalent linkage to graphene quantum dots proved to be functionally superior to π-π linkage, where singlet oxygen quantum yield value of the phthalocyanine in the membrane for the covalent linked conjugate was approximately twice that of the π-π stacked membrane.

Germanium triazatetrabenzcorrole and germanium phthalocyanine: Synthesis, fluorescence and singlet oxygen generation

The synthesis, fluorescence properties and singlet oxygen generation capability of germanium tetrabenzotriazacorrole (LGeTBC), germanium phthalocyanine (Cl[Formula: see text]GePc) and their derivatives are described. Measurements include UV-vis absorption spectra, fluorescence emission spectra, fluorescence quantum yields fluorescence lifetimes, and singlet delta oxygen quantum yields. LGeTBC and its derivatives exhibit quite different spectral and fluorescence properties from their phthalocyanine precursor. Both LGeTBC and Cl[Formula: see text]GePc show high singlet delta oxygen quantum yields and suitable fluorescence quantum yields, indicating that they can act as good singlet oxygen photosensitizers for photodynamic therapy.

Porphyrinic Ionic Liquid Dyes: Synthesis and Characterization.

Four porphyrinic ionic liquids and four higher melting salts (>100 °C) were synthesized as potential photosensitizers from highly symmetric porphyrins by introducing alkyl chains and exchanging anions to tune their solubility and singlet oxygen generation capability. Among the synthesized compounds was 5,10,15,20‐tetra(4‐dodecylpyridinum)porphyrin tetrakis‐bis(trifluoromethylsulfonyl)‐amide, a room‐temperature ionic liquid that could be crystallized as a solvate with nitrobenzene.

Supramolecular Confinement within Chitosan Nanocomposites Enhances Singlet Oxygen Generation.

The synthesis of water-soluble chitosan nanocomposites incorporating BODIPY and the investigation of their photosensitization properties is reported. It was observed that the singlet oxygen generation capability of nanocomposites containing a mixture of BODIPY and iodine-containing molecules are higher than that of the nanocomposites containing BODIPY alone. It is hypothesized that the supramolecular interactions between BODIPY and iodine-containing molecules confined within the nanocomposites lead to the enhanced singlet oxygen generation.

Synthesis of novel Chlorin e6-curcumin conjugates as photosensitizers for photodynamic therapy against pancreatic carcinoma

Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1H NMR, 13C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1 cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30 min and sustained for 24 h. Compound 17 showed excellent PDT efficacy with IC50 of 40, 35 and 41 nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371–7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients.

New porphyrin-based dendrimers with alkene linked fluorenyl antennae for optics

The biphotonic (σ2) singlet oxygen generation capability (ΦΔ) of new TFP-based photosensitizers peripherally functionalized with various dendrons containing 2-ethynylflorenyl chromophores is reported along with remarkable fluorescence yields (ΦF) of up to 17%.

The effects of bromine atoms on the photophysical and photochemical properties of 3-cinnamoylcoumarin derivatives

Coumarin derivatives modified using bromine atoms linked onto the right benzene ring (mainly in the HOMO) could enhance singlet oxygen generation capability.

Sizing Down a Supramolecular Gel into Micro- and Nanoparticles.

A low molecular weight gelator with a fluorescent 1,8-naphthalimide unit forms micro- and nanoparticles in aqueous media. Slow addition of a DMSO solution of the gelator into water affords either a self-assembled fibrillar network, sheaf-like microparticles, or nanoparticles depending to the concentration used in the experiment. The micro- and nanoparticles were characterized by dynamic light scattering (DLS), electron microscopy, and fluorescence measurements. In an initial assay of particle loading, Rose Bengal and Rhodamine 123 were shown to be incorporated in the particles. Light-promoted singlet oxygen generation capabilities of Rose Bengal were modulated by its incorporation in the particles. Additionally, the particles were found to promote the transport of Rhodamine 123 into human lung carcinoma live cells. These results indicate that nanoparticles arising from low molecular weight gelators may represent a new type of nanocarriers, being a potential alternative to polymeric nanogels used in nanomedicine.

Photoresponsive Supramolecular Polymer Networks via Hydrogen Bond Assisted Molecular Tweezer/Guest Complexation.

Noncovalent molecular recognition exerts significant impact on the structure and functionality of self-assembled materials. In this work, we have developed a novel strategy toward supramolecular polymer networks, with the utilization of molecular tweezer/guest complexation as the cross-linkages. Intermolecular O-H···N hydrogen bond is embedded in bis[alkynylplatinum(II)] terpyridine molecular tweezer/trans-azobenzene recognition motif, which could not only enhance the cross-linking strength, but also endow photoresponsiveness to the supramolecular network assemblies. Moreover, supramolecular polymer networks display intriguing singlet oxygen generation capability due to the inherent incorporation of organoplatinum(II) units. Hence, it offers a new avenue toward supramolecular materials via the combination of π-functionality, processability, and stimuli-responsiveness in an elaborate manner.

Novel Bodipy- triazine conjugates: Synthesis and the generation of singlet oxygen

Novel Bodipy decorated triazine conjugates were successfully designed and synthesized by the click reaction of azido functionalized di-styryl Bodipys with propargyl alkoxide substituted triazine. The identities of newly synthesized compounds were confirmed by using 1H and 13C NMR spectroscopies. The molecular structure of propargyl alkoxide substituted triazine was also determined by X-ray crystallography. The photophysical (fluorescence lifetime and fluorescence quantum yield) and photochemical (the singlet oxygen generation capabilities and appropriate photo degradation by light irradiation) properties of Bodipy- triazine conjugates were investigated for determination of their fluorescence and photosensitizer abilities. These results will provide further insight and motivation for development of Bodipy based singlet oxygen photosensitizer systems.

Polyethylene glycol phospholipids encapsulated silicon 2,3-naphthalocyanine dihydroxide nanoparticles (SiNcOH-DSPE-PEG(NH2) NPs) for single NIR laser induced cancer combination therapy

Currently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a powerful technique for cancer treatment. However, most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength, resulting in complex treatment process. In this work, a novel theranostic nanoplatform (SiNcOH-DSPE-PEG(NH2) NPs) has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide (SiNcOH) with DSPE-PEG and DSPE-PEG-NH2 for photoacoustic (PA) imaging-guided PTT and PDT tumor ablation for the first time. The as-prepared single-agent SiNcOH-DSPE-PEG(NH2) NPs not only have good water solubility and biocompatibility, but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808nm NIR laser irradiation. In addition, owing to their high absorption at NIR region, the SiNcOH-DSPE-PEG(NH2) NPs can also be employed as an effective diagnostic nanoagent for photoacoustic (PA) imaging. In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues. Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG(NH2) NPs into consideration, our study provides a promising strategy to realize molecular imaging-guided combination therapy.

Photophysical and photochemical properties of novel peripherally triethyleneoxysulfanyl substituted monomeric and Si–Si bonded dimeric silicon phthalocyanines

Monomeric and Si–Si bonded dimeric silicon(IV) phthalocyanines bearing 4[Formula: see text],7[Formula: see text],10[Formula: see text]-trioxaundecylsulfanyl groups were synthesized. These novel phthalocyanine derivatives were characterized by general analysis methods such as FT-IR, MALDI-TOF or HRMS, 1H NMR and UV-vis electronic absorption. Their aggregation behaviors were described in dimethyl sulfoxide (DMSO). In addition, the photophysical and photochemical properties of these phthalocyanines were also investigated in DMSO to determine potential of these phthalocyanines to acts as photosensitizer for photodynamic therapy (PDT) of cancer. Their high singlet oxygen generation demonstrated their suitability for PDT applications. These peripherally 4[Formula: see text],7[Formula: see text],10[Formula: see text]-trioxaundecylsulfanyl substituted silicon(IV) phthalocyanines are promising Type II photosensitizers owing to their favorable singlet oxygen generation capability. In addition, their fluorescence quenching behavior by 1,4-benzoquinone were also studied in DMSO.

Orthogonal Bodipy Trimers as Photosensitizers for Photodynamic Action.

Orthogonally linked BODIPY units show exceptional intersystem crossing efficiencies. We now report orthogonal BODIPY trimers with strong absorption in the visible region and high singlet oxygen generation capability. The X-ray diffraction structure confirms that the two peripheral BODIPY units are at a perpendicular angle to the core structure.

Novel phthalocyanine–BODIPY conjugates and their photophysical and photochemical properties

Novel zinc(II) phthalocyanines bearing boron dipyrromethene (BODIPY) (8) and its mono-styryl (9) and di-styryl (10) derivatives containing p-(N,N-diethylamino)benzaldehyde moieties were designed and synthesized for the first time. These phthalocyanines (8–10) were prepared by the copper-free Sonogashira coupling reaction of terminal ethynyl functionalized BODIPYs [4,4′-difluoro-8-(4-propynyloxy)-phenyl-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (2), 4,4′-difluoro-8-(4-propynyloxy)-phenyl-3,5,7-trimethyl-1-((4-diethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene (5), or 4,4′-difluoro-8-(4-propynyloxy)-phenyl-3,5-dimethyl-1,7-bis((4-4″-diethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene (6)] with tetrakis(iodo) zinc(II) phthalocyanine (7). All newly synthesized compounds were fully characterized by elemental analysis and general spectroscopic methods such as 1H NMR, FT-IR, mass, UV–Vis, and fluorescence. The photophysical (fluorescence quantum yields and lifetimes), photochemical (singlet oxygen generation capability and photodegradation behaviors) properties of these phthalocyanines were also investigated for determination of their photodynamic therapy (PDT). The results obtained indicated that these conjugates could be promising photosensitizers for PDT applications.