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Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age‐related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge. A β‐galactosidase (β‐gal)‐activated boron dipyrromethene (BODIPY)‐based photosensitizer (compound 1) is reported here that can selectively detect and eradicate senescent cells. It contains a galactose moiety connected to a pyridinium BODIPY via a self‐immolative nitrophenylene linker, of which the photoactivity is effectively quenched. Upon interactions with the senescence‐associated β‐gal, it undergoes enzymatic hydrolysis followed by self‐immolation, leading to the release of an activated BODIPY moiety by which the fluorescence emission and singlet oxygen generation are restored. The ability of 1 to detect and eliminate senescent cells is demonstrated in vitro and in vivo, using SK‐Mel‐103 tumor‐bearing mice treated with senescence‐inducing therapy. The results demonstrate that 1 can be selectively activated in senescent cells to trigger a robust senolytic effect upon irradiation. This study breaks new ground in the design and application of new senolytic agents based on photodynamic therapy. [ABSTRACT FROM AUTHOR]

An acetal-linked dimeric phthalocyanine has been synthesised and immobilised on the surface of gold nanobipyramids. The resulting nanocomposite serves as a highly sensitive probe for intracellular pH through its acid-responsive fluorescence and surface-enhanced Raman scattering signals. The phthalocyanine units released in the acidic intracellular environment can also effectively eliminate the cancer cells upon light irradiation, rendering this simple fabricated nanosystem a bimodal and bifunctional theranostic agent. [ABSTRACT FROM AUTHOR]

As an effective and non‐invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber‐optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post‐PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black‐hole quencher BHQ‐3 conjugated with a bicyclo[6.1.0]non‐4‐yne (BCN) moiety and a tetrazine‐substituted boron dipyrromethene‐based photosensitizer. By using tumor‐bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ‐3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT. [ABSTRACT FROM AUTHOR]

A water‐soluble 1,2,4,5‐tetrazine‐substituted carbon‐dipyrromethene (C–DIPY) was synthesized from the previously reported carbonyl pyrrole dimer through a two‐step procedure. Owing to the presence of a tetrazine moiety, the fluorescence emission of this compound was largely quenched in phosphate‐buffered saline at pH 7.4. Upon addition of a bicyclo[6.1.0]non‐4‐yne (BCN) derivative, the tetrazine‐based quenching component of the compound was disrupted through the inverse electron‐demand Diels‐Alder reaction to restore the fluorescence in up to 6.6‐fold. This bioorthogonal activation was also demonstrated using U‐87 MG human glioblastoma cells, in which the fluorescence intensity of this C–DIPY could be enhanced by 8.7‐fold upon post‐incubation with the BCN derivative. The results showed that this tetrazine‐caged C–DIPY can serve as a bioorthogonally activatable fluorescent probe for bioimaging. The compound, however, was found to reside preferentially in the lysosomes instead of the mitochondria of the cells as predicted based on its cationic character, which could be attributed to its energy‐dependent endocytic cellular uptake pathway, for which lysosomes are the end station. [ABSTRACT FROM AUTHOR]

Sodium‐ion batteries (SIBs) have attracted considerable interest as an alternative to lithium‐ion batteries owing to their similar electrochemical performance and superior long‐term cycle stability. Organic materials are regarded as promising anode materials for constructing SIBs with high capacity and good retention. However, utilization of organic materials is rather limited by their low energy density and poor stability at high current densities. To overcome these limitations, we utilized a novel polymeric disodium phthalocyanines (pNaPc) as SIB anodes to provide stable coordination sites for Na ions as well as to enhance the stability at high current density. By varying the linker type during a one‐pot cyclization and polymerization process, two pNaPc anodes with O‐ (O‐pNaPc) and S‐linkers (S‐pNaPc) were prepared, and their structural and electrochemical properties were investigated. The O‐pNaPc binds Na ions with a lower binding energy compared with S‐pNaPc, which leads to more facile Na‐ion coordination/dissociation when engaged as SIB anode. The use of O‐pNaPc significantly improves the redox kinetics and cycle stability and allows the fabrication of a full cell against Na3V2(PO4)2F3/C cathode, which demonstrates its practical application with high energy density (288 Wh kg−1) and high power density (149 W kg−1). [ABSTRACT FROM AUTHOR]

The utilisation of enzymes as stimuli can activate theranostic agents in a highly specific manner. We report herein a far-red-absorbing boron dipyrromethene-based photosensitiser that is responsive towards the cancer-associated human NAD(P)H:quinone oxidoreductase 1, enabling the controlled restoration of photodynamic activity for selective elimination of cancer cells. [ABSTRACT FROM AUTHOR]

A β-galactosidase-responsive photosensitiser has been designed and synthesised. It contains a galactosyl substrate, a boron dipyrromethene-based photosensitising unit and a black hole quencher 2 connected via an AB2-type self-immolative linker. This novel photosensitiser can be selectively activated by the senescence-associated β-galactosidase in senescent cells, leading to restoration in fluorescence emission and effective killing of the cells via photodynamic action. [ABSTRACT FROM AUTHOR]

A series of di‐α‐substituted zinc(II) phthalocyanines with different number of galactose moieties, ranging from 1 to 8, namely Pc‐galn (n=1, 2, 4, and 8) were designed and synthesized. The synthesis involved the copper‐catalyzed azide‐alkyne cycloaddition reaction of a mono‐ or dialkynyl zinc(II) phthalocyanine with an acetyl‐protected galactosyl azide or its dendritic derivative with four acetyl‐protected galactosyl groups, followed by removal of the acetyl protecting groups via alkaline hydrolysis. In N,N‐dimethylformamide, these oligogalactosyl phthalocyanines were non‐aggregated as shown by the strong Q‐band absorption and fluorescence emission. Owing to the di‐α‐substitution, they also behaved as efficient singlet oxygen generators upon light irradiation with a singlet oxygen quantum yield of 0.84. The spectroscopic and photophysical properties were not affected by the number of galactosyl units. In contrast, the compounds became significantly aggregated and quenched in phosphate‐buffered saline. Their cellular uptake was then studied using a range of cell lines, which generally followed the order Pc‐gal1>Pc‐gal2≈Pc‐gal4>Pc‐gal8. Interestingly, the di‐galactosyl analogue exhibited selective uptake against HeLa human cervical carcinoma cells through an energy‐dependent pathway instead of the expected asialoglycoprotein receptor. Upon light irradiation, it could effectively kill the cells with a half‐maximal inhibitory concentration of 0.58 μM. [ABSTRACT FROM AUTHOR]

Targeted delivery and specific activation of photosensitizers can greatly improve the treatment outcome of photodynamic therapy. To this end, we report herein a novel dual receptor‐mediated bioorthogonal activation approach to enhance the tumor specificity of the photodynamic action. It involves the targeted delivery of a biotinylated boron dipyrromethene (BODIPY)‐based photosensitizer, which is quenched in the native form by the attached 1,2,4,5‐tetrazine unit, and an epidermal growth factor receptor (EGFR)‐targeting cyclic peptide conjugated with a bicycle[6.1.0]non‐4‐yne moiety. Only for cancer cells that overexpress both the biotin receptor and EGFR, the two components can be internalized preferentially where they undergo an inverse electron‐demand Diels–Alder reaction, leading to restoration of the photodynamic activity of the BODIPY core. By using a range of cell lines with different expression levels of these two receptors, we have demonstrated that this stepwise "deliver‐and‐click" approach can confine the photodynamic action on a specific type of cancer cells. [ABSTRACT FROM AUTHOR]

Targeted delivery and specific activation of photosensitizers can greatly improve the treatment outcome of photodynamic therapy. To this end, we report herein a novel dual receptor‐mediated bioorthogonal activation approach to enhance the tumor specificity of the photodynamic action. It involves the targeted delivery of a biotinylated boron dipyrromethene (BODIPY)‐based photosensitizer, which is quenched in the native form by the attached 1,2,4,5‐tetrazine unit, and an epidermal growth factor receptor (EGFR)‐targeting cyclic peptide conjugated with a bicycle[6.1.0]non‐4‐yne moiety. Only for cancer cells that overexpress both the biotin receptor and EGFR, the two components can be internalized preferentially where they undergo an inverse electron‐demand Diels–Alder reaction, leading to restoration of the photodynamic activity of the BODIPY core. By using a range of cell lines with different expression levels of these two receptors, we have demonstrated that this stepwise "deliver‐and‐click" approach can confine the photodynamic action on a specific type of cancer cells. [ABSTRACT FROM AUTHOR]

A multifunctional photodynamic molecular beacon (PMB) has been designed and synthesized which contains an epidermal growth factor receptor (EGFR)‐targeting cyclic peptide and a trimeric phthalocyanine skeleton in which the three zinc(II) phthalocyanine units are each substituted with a glutathione (GSH)‐responsive 2,4‐dinitrobenzenesulfonate (DNBS) quencher and are linked via two cathepsin B‐cleavable GFLG peptide chains. This tailor‐made conjugate is fully quenched in the native form due to the photoinduced electron transfer effect of the DNBS moieties and the self‐quenching of the phthalocyanine units. It can target the EGFR overexpressed in cancer cells, and after receptor‐mediated endocytosis, it can be activated selectively by the co‐existence of intracellular GSH and cathepsin B, both of which are also overproduced in cancer cells, in terms of fluorescence emission and singlet oxygen generation. The cell‐selective behavior of this PMB has been demonstrated using a range of cancer cells with different expression levels of EGFR, while the stimuli‐responsive properties have been studied both in vitro and in various aqueous media. The overall results show that this advanced PMB, which exhibits several levels of control of the tumor specificity, is a promising photosensitizer for precise antitumoral photodynamic therapy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an established treatment modality for a range of superficial and localized cancers. There has been tremendous interest in the development of advanced photosensitizers that exhibit superior photophysical properties, high tumor selectivity, and improved pharmacokinetics. Glucose is one of the well-studied targeting moieties that can deliver various therapeutic agents to cancer cells selectively via the Warburg effect. However, the use of glucosylated photosensitizers for targeted PDT has remained little studied and to the best of our knowledge, the PDT effect of the positional isomers of these conjugates has never been compared. We report herein the preparation and photophysical properties of the C1α and C1β anomers of a glucosylated boron dipyrromethene-based photosensitizer. The cellular uptake and photocytotoxicity of both anomers were also studied and compared using A549 human lung carcinoma cells and HEK293 human embryonic kidney cells. Interestingly, the cellular uptake of the C1α anomer was approximately 2-fold higher than that of the C1β anomer regardless of the cell type and incubation time. The uptake pathway of both anomers was also studied. It was found that they were internalized through energy-dependent receptor/protein-mediated endocytosis rather than the well-known glucose transporters and sodium-driven glucose symporters. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a clinically approved treatment for various types of cancer. Besides killing the tumor cells directly, PDT has also been reported to trigger anti-tumor immunity. In our previous study, BAM-SiPc-based PDT was shown to induce immunogenic cell death on CT26 murine colon tumor cells in vitro. Using the BALB/c mouse animal model and a vascular-PDT (VPDT) approach, it could also eradicate tumor in ∼ 70% of tumor-bearing mice and elicit an anti-tumor immune response. In the present study, the serum obtained from the VPDT-cured mice was studied and found to possess various immunomodulatory properties. In in vitro studies, it stimulated cytokine secretions of IL-6 and C-X-C motif chemokine ligands 1–3 in CT26 cells through the NF-κB and MAPK pathways. The complement protein C5a boosted in the serum was shown to be involved in the process. The serum also induced calreticulin exposure on CT26 cells and activated dendritic cells. It contained CT26-targeting antibodies which, through the Fc region, induced macrophage engulfment of the tumor cells. In in vivo studies, inoculation of the serum-treated CT26 cells to mice demonstrated a retarded tumor growth with leukocytes, particularly T cells, attracted to the tumor site. In addition, the VPDT-cured mice showed different degrees of resistance against challenge of other types of murine tumor cells, for example, the breast tumor 4T1 and EMT6 cells. [ABSTRACT FROM AUTHOR]

A pH‐responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo‐I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo‐II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation. [ABSTRACT FROM AUTHOR]

Polymeric metal phthalocyanines have great potential as electrocatalysts, yet their incorporation on a current collector without losing the activity of metal centers remains a challenge. Herein, a new strategy for preparing a series of polymeric cobalt phthalocyanines containing S linkers (pCoPc‐1) or SO2 linkers (pCoPc‐2) and their tunable electrochemical properties are reported. The pCoPcs coated on various substrates show favorable electrocatalytic activities toward oxygen and hydrogen evolution reactions (OER and HER). Particularly, the pCoPc‐1 layer on Co3O4 nanosheet arrays exerts a cooperative effect enhancing both the OER and HER performances, and the subsequent phosphorization (P@pCoPc‐1/Co3O4|CC) significantly boosts the HER performance with enhanced hydrophilicity and conductivity. The high permeability and stability reinforcement of the pCoPc‐1 layer allow the phosphorization of underlying Co3O4 to CoP without degradation, which remarkably enhances OER and HER performances as manifested by low overpotentials of 320 and 120 mV at 10 mA cm−2, respectively. When engaged as a bifunctional electrocatalyst for the overall water splitting, the P@pCoPc‐1/Co3O4|CC requires a low cell voltage of 1.672 V at 10 mA cm−2, showing long‐term durability and mechanical robustness. This study demonstrates the collaborative catalytic role of polymeric macrocyclic compounds that offers versatile tunability and stability for various electrocatalytic reactions. [ABSTRACT FROM AUTHOR]

A nanoprobe based on polydopamine-coated gold nanobipyramids surface modified with molecules of a phenylboronic acid-substituted distyryl boron dipyrromethene has been fabricated and characterised using various physical and spectroscopic methods. It serves as an ultrasensitive sensor for sialic acids on the surface of cancer cells based on its dual surface-enhanced Raman scattering and fluorescence response. This biomarker can also trigger the photodynamic activity of these nanobipyramids, effectively eradicating the cancer cells mainly through apoptosis as shown by various bioassays. [ABSTRACT FROM AUTHOR]

Photocages for protection and the controlled release of bioactive compounds have been widely investigated. However, the vast majority of these photocages employ the cleavage of single bonds and high‐energy ultraviolet light. The construction of a photoactivation system that uses visible light to cleave unsaturated bonds still remains a challenge. Herein, we report a regioselective oxidative cleavage of C=C bonds from a boron‐dipyrrolemethene (BODIPY)‐based photocage by illumination at 630 nm, resulting in a free aldehyde and a thiol fluorescent probe. This strategy was demonstrated in live HeLa cells, and the generated α‐formyl‐BODIPY allowed real‐time monitoring of aldehyde release in the cells. In particular, it is shown that a mannose‐functionalized photocage can target HepG2 cells. [ABSTRACT FROM AUTHOR]

Two zinc(II) phthalocyanines substituted with two and four permethylated β-cyclodextrin moieties at the α positions have been synthesised and immobilised on the surface of adamantane-modified silica nanoparticles through host–guest interactions. These molecular and supramolecular systems can catalyse the photooxygenation of 1-naphthol and 2-furoic acid in organic and aqueous media with high conversion efficiency and reaction yield, and photodegradation of 2-chlorophenol in water. Having a higher photostability and recyclability, the supramolecular nanosystems are particularly promising for these photocatalytic applications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an anti-tumor modality which employs three individually non-toxic substances, including photosensitizer, light and oxygen, to produce a toxic effect. Besides causing damage to blood vessels that supply oxygen and nutrients to the tumor and killing the tumor by a direct cytotoxic effect, PDT has also been known to trigger an anti-tumor immune response. For instance, our previous study showed that PDT with BAM-SiPc, a silicon(IV) phthalocyanine based-photosensitizer, can not only eradicate the mouse CT26 tumor cells in a Balb/c mouse model, but also protect the mice against further re-challenge of the tumor cells through an immunomodulatory mechanism. To understand more about the immune effect, the biochemical actions of BAM-SiPc-PDT on CT26 cells were studied in the in vitro system. It was confirmed that the PDT treatment could induce immunogenic necroptosis in the tumor cells. Upon treatment, different damage-associated molecular patterns were exposed onto the cell surface or released from the cells. Among them, calreticulin was found to translocate to the cell membrane through a pathway similar to that in chemotherapy. The activation of immune response was also demonstrated by an increase in the expression of different chemokines. [ABSTRACT FROM AUTHOR]

A facile approach to assemble catalase‐like photosensitizing nanozymes with a self‐oxygen‐supplying ability was developed. The process involved Fe3+‐driven self‐assembly of fluorenylmethyloxycarbonyl (Fmoc)‐protected amino acids. By adding a zinc(II) phthalocyanine‐based photosensitizer (ZnPc) and the hypoxia‐inducible factor 1 (HIF‐1) inhibitor acriflavine (ACF) during the Fe3+‐promoted self‐assembly of Fmoc‐protected cysteine (Fmoc‐Cys), the nanovesicles Fmoc‐Cys/Fe@Pc and Fmoc‐Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe3+ could catalyze the transformation of H2O2 enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc‐Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc‐Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF. [ABSTRACT FROM AUTHOR]

A facile approach to assemble catalase‐like photosensitizing nanozymes with a self‐oxygen‐supplying ability was developed. The process involved Fe3+‐driven self‐assembly of fluorenylmethyloxycarbonyl (Fmoc)‐protected amino acids. By adding a zinc(II) phthalocyanine‐based photosensitizer (ZnPc) and the hypoxia‐inducible factor 1 (HIF‐1) inhibitor acriflavine (ACF) during the Fe3+‐promoted self‐assembly of Fmoc‐protected cysteine (Fmoc‐Cys), the nanovesicles Fmoc‐Cys/Fe@Pc and Fmoc‐Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe3+ could catalyze the transformation of H2O2 enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc‐Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc‐Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF. [ABSTRACT FROM AUTHOR]

A novel conjugate of a zinc(II) phthalocyanine with three 2,4-dinitrobenzenesulfonate (DNBS) substituents, a bis(ferrocenylethenyl) boron dipyrromethene (BODIPY) and a pyrene connected respectively via an acid-sensitive ketal bridge and a singlet oxygen-cleavable thioketal linker has been designed and synthesised. It is responsive towards four stimuli, including glutathione (GSH), acid and light sources at a wavelength of >610 nm and 345 nm in a sequence-dependent manner, enabling it to function as a molecular keypad lock with the four inputs. This work represents a proof-of-concept study using specially designed molecules to perform complicated sequential logic operations. [ABSTRACT FROM AUTHOR]

A novel synthetic strategy for in situ cyclisation of peptides and conjugation with functional boron dipyrromethenes (BODIPYs) has been developed. Linear peptides with up to 16 amino acid residues can be cyclised effectively and the resulting conjugates can be isolated in higher than 20% yield. One of the conjugates having a cyclic RGD moiety has been studied both in vitro and in vivo. It exhibits high and selective affinity towards the αvβ3-positive cell lines and induces high photocytotoxicity. The conjugate can also selectively localise in and effectively inhibit the growth of αvβ3-overexpressed tumour in vivo. [ABSTRACT FROM AUTHOR]

A combined stimulus-responsive photosensitiser and drug release system based on mesoporous silica nanoparticles was prepared. This nanoplatform encapsulated molecules of zinc(II) phthalocyanine substituted with a glutathione-cleavable 2,4-dinitrobenzenesulfonate quencher and doxorubicin linked via a singlet-oxygen-cleavable 9,10-dialkoxyanthracene linker. In the presence of glutathione (in mM range) and upon irradiation (λ > 610 nm), the phthalocyanine units were activated by detaching from the quenching component to emit fluorescence and generate singlet oxygen. The latter subsequently cleaved the 9,10-dialkoxyanthracene linker to trigger the release of a doxorubicin derivative. The glutathione- and light-controlled activation and drug-release processes on this nanoplatform were demonstrated in phosphate buffered saline. The activation in fluorescence emission by intracellular thiols was also shown inside HepG2 human hepatocellular carcinoma cells. Upon irradiation, the nanosystem exhibited high cytotoxicity due to the photodynamic effect of the activated phthalocyanine units, but the cytotoxic effect of the released Dox moieties was not notable probably due to their reduced cytotoxicity as a result of the pendant substituent and the low drug loading in the nanoparticles. [ABSTRACT FROM AUTHOR]

Phthalocyanines exhibit superior photoproperties that make them a surely attractive class of photosensitisers for photodynamic therapy of cancer. Several derivatives are at various phases of clinical trials, and efforts have been put continuously to improve their photodynamic efficacy. To this end, various strategies have been applied to develop advanced phthalocyanines with optimised photoproperties, dual therapeutic actions, tumour-targeting properties and/or specific activation at tumour sites. The advantageous properties and potential of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer are highlighted in this tutorial review. [ABSTRACT FROM AUTHOR]

A boron dipyrromethene based photosensitiser substituted with a 1,2,4,5-tetrazine moiety has been prepared of which the photoactivity can be activated upon an inverse-electron-demand Diels–Alder reaction with trans-cyclooctene derivatives. By using a biotin-conjugated trans-cyclooctene to tag the biotin-receptor-positive HeLa cells, this photosensitiser exhibits site-specific activation through cycloaddition, leading to high photocytotoxicity. [ABSTRACT FROM AUTHOR]

This Special Collection on Photodynamic Therapy highlights part of the research endeavours aiming to enhance our understanding on the structure-property relationship of photosensitizers, improve their photo-physical and biological properties, extend the applications of PDT, and beyond. Guest Editors Pui-Chi Lo, Dennis Ng, Ravindra Pandey, and Petr Zimcik introduce the Special Collection on Photodynamic Therapy and give an overview of the developments and challenges in this exciting field. [Extracted from the article]

A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice. [ABSTRACT FROM AUTHOR]

An efficient near‐infrared‐absorbing dark quencher based on ferrocenyl boron dipyrromethene (BODIPY) has been developed and used to construct a fluorescence resonance energy transfer (FRET)‐based activatable photosensitizer. This smart photosensitizer contains a zinc(II) phthalocyanine as the photosensitizing unit which is conjugated to this dark quencher through a glutathione‐cleavable disulfide linker. The photoactivities of the phthalocyanine unit are largely quenched through FRET to the BODIPY unit followed by photoinduced electron transfer from the attached ferrocenyl moiety. Upon exposure to glutathione in phosphate buffered saline and inside HT29 human colorectal adenocarcinoma cells, the fluorescence emission and singlet oxygen generation efficiency of the photosensitizer are significantly enhanced due to cleavage of the disulfide bond and detachment of the dark quencher from the photosensitizing unit. The activation in fluorescence emission has also been demonstrated in tumor‐bearing nude mice. The glutathione‐responsive behavior has been verified by comparison with the negative results of a non‐cleavable analogue. The results suggest that ferrocenyl BODIPYs could serve as tailorable dark quenchers and the disulfide‐linked phthalocyanine–quencher conjugate acts as an efficient glutathione‐activated photosensitizer for photodynamic therapy. [ABSTRACT FROM AUTHOR]

Mosquitoes are significant vectors, responsible for transmitting serious infectious diseases, including the recent epidemics of global significance caused by, for example, Zika, Dengue and Chikungunya viruses. The chemical insecticides in use for mosquito control are toxic and ineffective due to the development of resistance to them. The new approach to reduce mosquito population by releasing genetically modified males to cause female infertility is still under environmental safety evaluation. Photodynamic insecticides (PDI) have long been known as a safe and effective alternative by using dyes as the photosensitizers (PS) for activation with light to generate insecticidal singlet oxygen and reactive oxygen species. This approach warrants re-examination with advances in the chemical synthesis of novel PS, e.g. phthalocyanines (PC). Nine PC were compared with five porphyrin derivatives and two classic PS of halogenated fluoresceins, i.e. cyanosine and rose bengal experimentally for photodynamic treatment (PDT) of the larvae of laboratory-reared Aedes mosquitoes and their cell lines. Groups of 2nd instar larvae were first exposed overnight to graded concentrations of each PS in the dark followed by their exposure to dim light for up to 7 hours. Larvae of both experimental and control groups were examined hourly for viability based on their motility. Monolayers of mosquito cells were similarly PS-sensitized and exposed briefly to light at the PS-specific excitation wavelengths. Cell viability was assessed by MTT reduction assays. Of the 16 PS examined for photodynamic inactivation of the mosquito larvae, effective are three novel PC, i.e. amino-Si-PC1 and -PC2, anilinium Zn-PC3.4, pyridyloxy Si-PC14 and two porphyrin derivatives, i.e. TPPS2 and TMAP. Their EC50 values were determined, all falling in the nanomolar range lower than those of rose bengal and cyanosine. All PS effective in vivo were also found to dose-dependently inactivate mosquito cells photodynamically in vitro, providing cellular basis for their larvicidal activities. The present findings of novel PC with effective photodynamic larvicidal activities provide fresh impetus to the development of PDI with their established advantages in safety and efficacy. Toward that end, the insect cell lines are of value for rapid screening of new PC. The optimal excitability of PC with insect-invisible red light is inferred to have the potential to broaden the range of targetable insect pests. [ABSTRACT FROM AUTHOR]

By using a copper‐promoted alkyne–azide cycloaddition reaction, two boron dipyrromethene (BODIPY) derivatives bearing a bis(1,2,3‐triazole)amino receptor at the meso position were prepared and characterized. For the analogue with two terminal triethylene glycol chains, the fluorescence emission at 509 nm responded selectively toward Hg2+ ions, which greatly increased the fluorescence quantum yield from 0.003 to 0.25 as a result of inhibition of the photoinduced electron transfer (PET) process. By introducing two additional rhodamine moieties at the termini, the resulting conjugate could also detect Hg2+ ions in a highly selective manner. Upon excitation at the BODIPY core, the fluorescence emission of rhodamine at 580 nm was observed and the intensity increased substantially upon addition of Hg2+ ions due to inhibition of the PET process followed by highly efficient fluorescence resonance energy transfer (FRET) from the BODIPY core to the rhodamine moieties. The Hg2+‐responsive fluorescence change of these two probes could be easily seen with the naked eye. The binding stoichiometry between the probes and Hg2+ ions in CH3CN was determined to be 1:2 by Job′s plot analysis and 1H NMR titration, and the binding constants were found to be (1.2±0.1)×1011 m−2 and (1.3±0.3)×1010 m−2, respectively. The overall results suggest that these two BODIPY derivatives can serve as highly selective fluorescent probes for Hg2+ ions. The rhodamine derivative makes use of a combined PET‐FRET sensing mechanism which can greatly increase the sensitivity of detection. PET‐FRET project: Two click‐derived BODIPY derivatives bearing a bis(1,2,3‐triazole)amino receptor have been prepared and investigated for their Hg2+‐sensing properties. Upon binding with Hg2+ ions, a strong emission was observed due to inhibition of the photoinduced electron transfer (PET) process in the BODIPY core or coupling with fluorescence resonance energy transfer (FRET) from the excited BODIPY core to the rhodamine moieties, resulting in a large Stokes shift. [ABSTRACT FROM AUTHOR]

Condensation of 1,8‐diamino‐3,6‐dichlorocarbazole with a series of disubstituted 1,3‐diiminoisoindolines, followed by treatment with BF3⋅OEt2 led to the formation of the corresponding core‐expanded boron(III) subphthalocyanine analogues. These air‐stable π‐conjugated boron(III) carbazosubphthalocyanines possess two boron‐containing seven‐membered‐ring units and a 16 π‐electron skeleton, and represent the first examples of antiaromatic boron(III) subphthalocyanine analogues as supported by spectroscopic and theoretical studies. The molecular structure of one of these compounds was unambiguously determined by single‐crystal X‐ray diffraction analysis. In contrast to typical boron(III) subphthalocyanines, which adopt a cone‐shaped structure, the π skeleton of this compound is almost planar. Core competencies: A series of novel core‐expanded boron(III) subphthalocyanine analogues, namely boron(III) carbazosubphthalocyanines, have been synthesized and characterized. They represent the first examples of antiaromatic boron(III) subphthalocyanine derivatives and the smallest antiaromatic azaporphyrinoids reported thus far. [ABSTRACT FROM AUTHOR]

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A series of pyrrolopyrrole aza boron dipyrromethene derivatives have been designed and synthesised as two-photon fluorescent probes. The bisalkynyl analogues, having a donor–π–donor quadrupolar skeleton, show a red-shifted Q band at ca. 700 nm in toluene and a two-photon absorption (TPA) cross-section up to 2349 GM at 1040 nm. To enable these dyes to be used for subcellular imaging, a branched oligoethylene glycol unit has been introduced to enhance their hydrophilicity and biocompatibility, and a potential organelle-selective group, namely triphenylphosphonium or morpholine moiety has also been added with a view to targeting the mitochondria or lysosomes respectively. The resulting conjugates are essentially non-aggregated in deionised water, exhibiting an intense Q band at 668 nm and a TPA cross-section up to 384 GM at 1040 nm. These spectral features have been analysed using density functional theory calculations, which suggest that the TPA is mainly due to the S0→ S2 transition. In the subcellular imaging study, it has been found that the triphenylphosphonium-containing derivative can localise in the lysosomes of HeLa human cervical carcinoma cells, which may be a result of its positive charge and the negative log P value (−2.46, P = partition coefficient), while the morpholine-substituted analogue does not exhibit preferential subcellular localisation. [ABSTRACT FROM AUTHOR]

Two hydrophilic aza-boron dipyrromethene (aza-BODIPY) derivatives have first been designed and synthesised for subcellular imaging. With a triphenylphosphonium or morpholine substituent, these probes show high affinity towards the mitochondria or lysosomes of a range of cancer cell lines, including human cervical cancer HeLa cells, hepatocellular carcinoma HepG2 cells, breast cancer MCF-7 cells and colon adenocarcinoma HT29 cells as revealed by confocal microscopy. By introducing two bromo groups into the aza-BODIPY skeleton, which can promote intersystem crossing by the heavy-atom effect, the resulting compounds become efficient singlet-oxygen generators and can serve as organelle-specific photosensitisers for photodynamic therapy (PDT). Upon irradiation, both compounds are photocytotoxic. The lysosome-targeted derivative exhibits higher cellular uptake and more efficient reactive oxygen species generation inside HeLa cells, resulting in higher PDT efficacy with an IC50 value of 0.48 μM and cell death mainly through apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: A series of disulfide‐linked dendritic phthalocyanines were synthesized by using the CuI‐catalyzed alkyne–azide cycloaddition reaction as the key step. Whereas these compounds were essentially nonaggregated in N,N‐dimethylformamide, they were stacked in citrate solution (pH 7.4, with 1 % Cremophor EL), as shown by the broad appearance of their Q‐band absorption. Having two‐to‐six zinc(II) phthalocyanine units in a molecule, these compounds were significantly self‐quenched, particularly in citrate solution. Both the fluorescence intensity and singlet‐oxygen generation efficiency were significantly lower than those of the monomeric counterparts, and the self‐quenching efficiency increased as the number of phthalocyanine units increased. Upon interaction with 5 m m glutathione (GSH) in citrate solution, the fluorescence intensity of these compounds increased as a result of cleavage of the disulfide linkages and separation of the phthalocyanine units, which thereby reduced the self‐quenching effect. The “on/off” ratios were found to be 7, 18, 23, and 21 for the dimeric (PC2), trimeric (PC3), tetrameric (PC4), and hexameric (PC6) systems, respectively. GSH also enhanced the fluorescence emission inside human colon adenocarcinoma HT29 cells and promoted the formation of singlet oxygen of these compounds. Upon irradiation, their half maximal inhibitory concentration (IC50) values were found to be in the range of 0.18 to 0.38 μ m. Finally, the biodistribution and activation of PC2 and PC6 were also examined in HT29 tumor‐bearing nude mice. For both compounds, the fluorescence intensity per unit area at the tumor was found to grow gradually during the first 24 h. Whereas the intensity then dropped for PC2, the intensity for PC6 remained steady over the following 6 d, which might have been a result of the enhanced permeability and retention effect arising from the larger molecular mass of the hexameric system. [ABSTRACT FROM AUTHOR]