Efficient Photosensitizers For Photodynamic Therapy Research Articles

Thio and Seleno Derivatives of Angelicin as Efficient Triplet Harvesting Photosensitizers: Implications in Photodynamic Therapy.

Photodynamic therapy (PDT) is widely accepted in medical practice for its targeted induction of apoptosis in cancerous cells. Angelicin (Ang) has traditionally been known for its efficacy in cancer treatment and its capability to enter a photoexcited triplet state. This study has comprehensively assessed the effects of substituting individual chalcogen atoms at three specific positions in Angelicin, with the objective of facilitating access to this elusive triplet state to enhance its role as a photosensitizer in PDT. The study scrutinizes various enhancements and factors that are crucial for efficient triplet harvesting. The decrease in singlet-triplet energy gap (ΔEST) and increased spin-orbit coupling (SOC) values present numerous viable pathways for intersystem crossing (ISC), leading to the triplet manifold. The lifetime of ISC, thus, decreases from 10-5 s-1 in Ang to 10‑8 s-1 in thioangelicin (TAng) and finally to 10-9 s-1 in selenoangelicin (SeAng). Additionally, this study investigates the two-photon absorption properties of thio and seleno-substituted Angelicin for their potentialities as non-UV photosensitizers. The interplay between electron-withdrawing and electron-donating substitutions in these derivatives significantly enhances the two-photon absorption cross-sections (σ) to as high as 49.3 GM while shifting the absorption wavelengths towards the infrared region enabling them as efficient PDT photosensitizers.

Nitrogen-doped carbon dots as a highly efficient photosensitizer for photodynamic therapy to promote apoptosis in oral squamous cell carcinoma

Photodynamic (PDT) is a new strategy for non-invasive tumor therapy and has been studied for the treatment of oral cancer. PDT has the advantages of low damage and high therapeutic efficiency. However, conventional photosensitizers have defects in different degrees, such as low stability and solubility, and low oxygen quantum yield of singlet oxygen. These defects greatly limit the efficiency of PDT. Several studies have shown that carbonaceous nanomaterials, carbon dots (CDs), are promising as a novel nanoscale photosensitizer to mediate PDT for cancer treatment. In this study, we utilized fluorescent CDs doped with nitrogen to optimize their photosensitizing activity to enhance PDT in oral squamous cell carcinoma (OSCC). Nitrogen-doped CDs were able to generate a large amount of reactive oxygen species (ROS) under 660-nm laser irradiation after uptake by cancer cells, effectively inducing apoptosis in the mitochondrial pathway. The in vivo and in vivo experiments verified that CDs-mediated PDT was able to promote apoptosis of tumor cells in terms of DNA damage, inhibition of angiogenesis and cell proliferation, etc. CDs, as a novel photosensitizer, is expected to be an outstanding tool for clinical PDT in the treatment of OSCC.

A structure-guided strategy to design Golgi apparatus-targeted type-I/II aggregation-induced emission photosensitizers for efficient photodynamic therapy

The Golgi apparatus (GA) is a vital target for anticancer therapy due to its sensitivity against reactive oxygen species (ROS)-induced oxidative stress that could lead to cell death. In this study, we designed a series of aggregation-induced emission (AIE)-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) carrying different ROS with selective GA-targeted ability. The in vitro study showed that TPAPyTZ and TPAPyTC displayed strong AIE characteristics, robust type-I/II ROS production capabilities, specific GA-targeted, high photostability, and high imaging quality. The cell-uptake of TPAPyTZ was found primarily through an energy-dependent caveolae/raft-mediated endocytosis pathway. Remarkably, TPAPyTZ induced GA-oxidative stress, leading to GA fragmentation, downregulation of GM130 expression, and activation of mitochondria caspase-related apoptosis during photodynamic therapy (PDT). In vivo experiments revealed that TPAPyTZ significantly inhibited tumor proliferation under lower-intensity white light irradiation with minimal side effects. Overall, our work presents a promising strategy for designing AIEgens for fluorescence imaging-guided PDT. Additionally, it enriched the collection of GA-targeted leads for the development of cancer theranostics capable of visualizing dynamic changes in the GA during cancer cell apoptosis, which could potentially enable early diagnosis applications in the future. Statement of significanceAIE luminogens (AIEgens) are potent phototheranostic agents that can exhibit strong fluorescence emission and enhance ROS production in the aggregate states. In this study, through the precise design of photosensitizers with four different electron-acceptors, we constructed a series of potent AIEgens (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) with strong fluorescence intensity and ROS generation capacity. Among them, TPAPyTZ with an extended π-conjugation displayed the strongest ROS generation ability and anti-tumor activity, resulting in an 88 % reduction in tumor weight. Our studies revealed that the enhanced activity of TPAPyTZ may be due to its unique Golgi apparatus (GA)-targeted ability, which causes GA oxidative stress followed by effective cancer cell apoptosis. This unique GA-targeted feature of TPAPyTZ remains rare in the reported AIEgens, which mainly target organelles such as lysosome, mitochondria, and cell membrane. The successful design of a GA-targeted and potent AIEgen could enrich the collection of GA-targeted luminogens, providing a lead theranostic for the further development of fluorescence imaging-guided PDT, and serving as a tool to explore the potential mechanism and discover new GA-specific drug targets.

N-bridging tetra-substituted zinc(II) phthalocyanines with Q-band absorption up to 780 nm and eminent photosensitizing activities for photodynamic therapy

With a view to developing highly efficient photosensitizers for photodynamic therapy, herein, we prepared a series of tetra-substituted zinc(II) phthalocyanine analogues (ZPOP, ZPSP, ZPNP, and ZPNPM) modified with O-, S-, and N-bridging substituents, respectively. Compared to O- and S-bridging analogues, the N-bridging phthalocyanines showed eminent red-shifted Q band absorption (750–780 nm) and excellent reactive oxygen species (ROS) generation ability (ΦΔ = 0.90–0.97), due to the HOMO destabilization, as well as the smaller ΔEST. To improve the hydrophility and biocompatibility, we further prepared two N-bridging zinc(II) phthalocyanines (ZPN1 and ZPN2) modified with morpholine and N,N-dimethylamine moieties, respectively, along with their quaternized counterparts (QZPN1 and QZPN2). These compounds exhibited NIR-absorbing Q bands at 774–777 nm and efficient ROS generation ability in aqueous solutions, especially formulated with 1 % Cremophor EL (Cel). In vitro studies indicated that ZPN2 exhibited the highest photodynamic activity against HepG2 cells (IC50 = 0.44 ± 0.02 μM), because of superior cellular uptake and moderate ROS generation ability. Moreover, ZPN2 could selectively accumulate and retain in tumor tissue of H22 tumor-bearing mice. The work presents a new strategy for the development of NIR-absorbing photosensitizers.

Squaraine-containing polymeric nanoparticles enable photodynamic and photothermal therapy of cancer cells

Herein, we unveil the synthesis and characterization of a squaraine (Sq1) and Pluronic F127 based Sq1@F127 nanoparticles. These nanoparticles exhibited fascinating photothermal and photodynamic properties. Experimental results showed that Sq1 was efficient photosensitizers that could produce reactive oxygen species (ROS) with singlet oxygen quantum yield of 0.019. Furthermore, we found that Sq1@F127 nanoparticles could increase the local temperature gradually from 24.0 °C to 54.2 °C over the course of 10 min. Sq1@F127 nanoparticles had a photothermal efficiency of 52%. Finally, in vitro phototherapy efficiency of Sq1@F127 nanoparticles were elucidated using human melanoma cells (SK-MEL 30/An1). Sq1@F127 nanoparticles did not exhibit any discernible toxicity in the dark. For photodynamic therapy (PDT), SK-MEL 30 cells were illuminated with red light, which was followed by laser irradiation (808 nm, 1.0 W/cm2) for photothermal therapy (PTT). It is noteworthy that up to 57% of melanoma cells could be killed by Sq1@F127 nanoparticles when dual therapy was carried out. Our data clearly showed that the treatment of Sq1@F127 nanoparticles with two different wavelengths produced a combined dual phototherapy effect on cancer cells. Overall, Sq1@F127 nanoparticles were truly efficient photosensitizers for PDT and PTT.

Fabrication and characterization of dissolving microneedles for transdermal delivery of hypocrellin A

Hypocrellin A (HA) is an efficient photosensitizer for photodynamic therapy in recent years. In order to improve the delivery of this photosensitizer, dissolving HA microneedles were established. Firstly, dissolving microneedles were prepared from HA by a two-step solvent casting method. Then, the dissolving HA microneedle were characterized by stereomicroscope, laser confocal microscope, scanning electron microscope, differential scanning calorimeter (DSC), X-ray diffractometer (XRD) and fourier infrared spectrometer (FTIR). Finally, the transdermal cumulative penetration experiments were conducted. The results showed that the dissolving HA microneedle has a conical shape with an average height of 650 μm. The mechanical strength endure a force of 44.78 N, resulting in 0.20 N per needle. The in vitro transdermal experiment showed that the dissolving HA microneedle almost completely dissolved in 5 min after insertion into the mouse skin. The depth of drug penetration through the skin can reach 601.36 μm. Moreover, the dissolving HA microneedle significantly improved the cumulative transdermal penetration efficiency of the photosensitizer through the skin. Therefore, the present study successfully established a dissolving microneedle of HA, which can quickly dissolve and significantly improve the transdermal delivery efficiency of HA.

Structural engineering of mitochondria-targeted Au-Ag2S photosensitizers for enhanced photodynamic and photothermal therapy.

Much effort has been devoted to designing diverse photosensitizers for efficient photodynamic therapy (PDT) and photothermal therapy (PTT) performance. However, the effect of PS morphology on the PDT and PTT performance needs to be further explored. In this work, a photosensitizer, Au-Ag2S nanoparticles functionalized with indocyanine green, caspase-3 recognition peptides, and mitochondria-targeting peptides (AICM NPs) with different morphologies, including core-shell, eccentric core-shell-I, eccentric core-shell-II, and Janus morphologies, were synthesized to enhance PDT and PTT performance. Among them, AICM Janus NPs with enhanced charge-transfer efficiency and photothermal conversion demonstrate superior PDT and PTT performance compared to those of other morphologies. In addition, AICM NPs exhibit satisfactory surface-enhanced Raman scattering performance for in situ SERS monitoring of caspase-3 during PDT and PTT processes. After PDT and PTT treatment with AICM Janus NPs, the damaged mitochondria released caspase-3. AICM Janus NPs achieved a superior apoptosis rate in tumor cells in vitro. Furthermore, AICM Janus NPs treat the tumors in vivo within only 10 days, which is half the time reported in other work. The AICM NPs demonstrated superior therapeutic safety both in vitro and in vivo. This study investigates the effects of morphology-property-performance of photosensitizers on the PDT and PTT performances, which opens a new pathway toward designing photosensitizers for efficient PDT and PTT.

Synthesis and evaluation of novel meso-substitutedphenyl dithieno[3,2-b]thiophene-fused BODIPY derivatives as efficient photosensitizers for photodynamic therapy

The discovery of new photosensitizer drugs with long wavelength Uv–vis absorption, high efficiency and low side-effects is still a challenge in photodynamic therapy. Here a series of novel meso-substitutedphenyl thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. All these compounds have strong absorption at 640–680 nm and obvious fluorescence emission at 650–760 nm. They exhibited high singlet oxygen generation ability and significant photodynamic efficiency against Eca-109 cancer cells. Compounds II4, II6, II9, II10 and II13 could generate intracellular ROS and induce cell apoptosis after laser irradiation, which displayed superior photodynamic efficiency against Eca-109 cells than Temoporfin in vitro and in vivo. Among them, compound II4 specifically exhibited excellent anti-tumor efficacy, and could be selected as a new drug candidate for PDT.

A silyl porphyrin derivative conjugated with 6-deoxy-6-sulfo-α-d-glucopyranose functions as an efficient photosensitizer for photodynamic therapy

We synthesized a new silyl porphyrin derivative conjugated with 6-deoxy-6-sulfo-α-d-glucopyranose (SGlc). Conjugation with SGlc improved A549 cellular uptake without significant changes in the photophysical and photochemical properties and subcellular localization. This improved cellular uptake led to enhanced photodynamic activity. Furthermore, conjugation with SGlc suppressed dark toxicity. These advantages were not observed for a conjugate with a glucose molecule. These results indicated that the conjugation with SGlc is a promising strategy for enhancing photodynamic efficacy.

Volatiles of Shiraia fruiting body-associated Pseudomonas putida No.24 stimulate fungal hypocrellin production

Hypocrellins are major bioactive perylenequinones from Shiraia fruiting bodies and have been developed as efficient photosensitizers for photodynamic therapy. Pseudomonas is the second dominant genus inside Shiraia fruiting bodies, but with less known actions on the host fungus. In this work, the effects of bacterial volatiles from the Shiraia-associated Pseudomonas on fungal hypocrellin production were investigated. Pseudomonas putida No.24 was the most active to promote significantly accumulation of Shiraia perylenequinones including hypocrellin A (HA), HC, elsinochrome A (EA) and EC. Headspace analysis of the emitted volatiles revealed dimethyl disulfide as one of active compounds to promote fungal hypocrellin production. The bacterial volatiles induced an apoptosis in Shiraia hyphal cell, which was associated with the generation of reactive oxygen species (ROS). ROS generation was proved to mediate the volatile-induced membrane permeability and up-regulation of gene expressions for hypocrellin biosynthesis. In the submerged volatile co-culture, the bacterial volatiles stimulated not only HA content in mycelia, but also HA secretion into the medium, leading to the enhanced HA production to 249.85 mg/L, about 2.07-fold over the control. This is the first report on the regulation of Pseudomonas volatiles on fungal perylenequinone production. These findings could be helpful to understand the roles of bacterial volatiles in fruiting bodies and also provide new elicitation method using bacterial volatiles to stimulate fungal secondary metabolite production.

Concise nanotherapeutic modality for cancer involving graphene oxide dots in conjunction with ascorbic acid.

Cancer cells tend to have higher intracellular reactive oxygen species (ROS) levels and are more vulnerable to ROS-generating therapies such as ascorbic acid (H2Asc) therapy, whose potency has been explored by several clinical trials. However, its efficiency is restricted by the requirement of pharmacologically high local H2Asc concentrations. Here, we show that nitrogen-doped graphene oxide dots (NGODs), which are highly crystalline and biocompatible, can serve as a catalytic medium for improving H2Asc cancer therapy at orally achievable physiological H2Asc concentrations. NGODs catalyze H2Asc oxidation for H2O2 and dehydroascorbic acid generation to disrupt cancer cells by consuming intracellular glutathione (GSH) and inducing ROS damage. This is the first study to demonstrate the direct consumption of GSH using a carbon-based nano-catalyst (NGODs), which further expedites tumor killing. In addition, as in our previous study, NGODs can also serve as a highly efficient photosensitizer for photodynamic therapy. Under illumination, NGODs produce a considerable amount of H2O2 in the presence of physiological levels of H2Asc as a hole scavenger and further enhance the therapeutic efficiency. Thus, a concise nanotherapeutic modality could be achieved through the conjunction of multifunctional NGODs and H2Asc to selectively eliminate deep-seated and superficial tumors simultaneously (under 65% of normal cell viability, it kills almost all cancer cells). Note that this level of therapeutic versatility generally requires multiple components and complex manufacturing processes that run into difficulties with FDA regulations and clinical applications. In this study, the concise NGOD-H2Asc nanotherapeutic modality has demonstrated its great potential in cancer therapy.

Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia.

Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O2-) as type I ROS. In particular, the primary precursor (˙O2-) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber-Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor-acceptor system, anion-π+ incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.

AIE-active Ir(III) complexes as type-I dominant photosensitizers for efficient photodynamic therapy.

The ability of a photosensitizer (PS) to generate reactive oxygen species (ROS) including type I oxygen free radicals and type II 1O2 is pivotal for photodynamic therapy. Luminescent Ir(III) complexes are effective PSs with high 1O2 generation ability owing to their high intersystem crossing ability and effective energy transfer to 3O2. However, so far, reports on type I ROS based on ˙OH generation induced by Ir(III) PS are still rare. In this work, four novel aggregation-induced emission (AIE)-active Ir(III) PSs, namely MFIriqa, MFIrqa, SFIriqa, and SFIrqa have been designed and synthesized, which show highly efficient emission in the aggregated state. Cell imaging experiment results indicate that all four Ir(III) PSs can effectively improve the signal-to-noise ratio of imaging by reducing the interference from the background due to their fascinating AIE properties. Importantly, in vitro, Ir(III) PSs MFIrqa, SFIriqa, and SFIrqa nanoparticles show obvious photodynamic activity toward cancer cells upon irradiation accompanied by type I ˙OH generation, which may be attributed to the unique excited-state characteristics of Ir(III) complexes. This work will provide guidance for the construction of a type I photosensitizer based on the AIE-active Ir(III) complex, which offers great advantages for potential clinical applications under hypoxic conditions.

Conjugates of lactobionic acid and IR820: New photosensitizers for efficient photodynamic therapy of hepatoma cells.

New indocyanine green (IR820) is an indocyanine green analog which has attracted increasing attention in cancer phototherapy for the prominent absorbance at near-infrared region and improved stability. However, the lack of tumor targeting ability is still an obstacle that severely limits the application of IR820. Lactobionic acid (LA) is a ligand for the asialoglycoprotein receptors which are overexpressed on the membrane of hepatocellular carcinoma cells. In this work, three conjugates of LA and IR-820, namely LA-IR820, LA-SS-IR820, and LA-DEG-IR820, were developed for targeted photodynamic therapy of hepatocellular carcinoma (HCC). The in vitro photodynamic effect study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit similar singlet oxygen quantum yield as compared to free IR820. The cellular uptake study demonstrates that LA-IR820, LA-SS-IR820, and LA-DEG-IR820 exhibit enhanced cellular uptake amount as compared to free IR820 due to the ligand-receptor interactions between LA and asialoglycoprotein receptor overexpressed on the membrane of HepG2 cells. Among these three conjugates, LA-IR820 with hydrodynamic diameter of 154.6 ± 6.1 nm exhibits the highest cellular uptake amount. The cellular reactive oxygen species (ROS) generation study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 display enhanced cellular ROS level as compared to free IR820 and LA-IR820 exhibits the highest cellular ROS level upon 600 mW/cm2 660 nm laser irradiation. As a result, LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit enhanced photocytotoxicity against HepG2 cells as compared to free IR820 and LA-IR820 exhibits the highest photocytotoxicity. LA-IR820, LA-SS-IR820, and LA-DEG-IR820 show significant potential for the targeted photodynamic therapy of HCC.

Recent Advances in Hypoxia-Overcoming Strategy of Aggregation-Induced Emission Photosensitizers for Efficient Photodynamic Therapy.

Hypoxia is an inherent physiologic barrier in the microenvironment of solid tumor and has badly restricted the therapeutic effect of photodynamic therapy (PDT). Meanwhile, the photosensitizer (PS) agents used for PDT applications regularly encounter the tiresome aggregation-caused quenching effect that seriously decreases the production efficiency of cytotoxic reactive oxygen species. The aggregation-induced emission (AIE) PSs with antiquenching characteristics in the aggregate state are considered as a promising tool for achieving highly efficient PDT applications, and plenty of studies have widely demonstrated their advantages in various diseases. Herein, the recent progress of AIE PSs in the battle of antitumor hypoxia issue is summarized and the practical molecular principles of hypoxia-overcoming AIE PSs are highlighted. According to the hypoxia-overcoming mechanism, these representative cases are divided into low O2 -dependent (type I PDT) and O2 -dependent tactics (mainly including O2 -enrichment type II PDT and combination therapy). Furthermore, the underlying challenges and prospects of AIE PSs in hypoxia-overcoming PDT are proposed and thus expect to promote the next development of AIE PSs.

Peripherally Crowded Cationic Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy.

Photodynamic therapy is a treatment modality of cancer based on the production of cytotoxic species upon the light activation of photosensitizers. Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy substituents were synthesized, and pyridyl moieties were methylated. The quaternized derivatives did not aggregate at all in water and retained their good photophysical properties. High photodynamic activity of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926 cells with a very low EC50 of 50 nM (for the MCF-7 cell line) upon light activation while maintaining low toxicity in the dark (TC50 ≈ 600 μM), giving thus good phototherapeutic indexes (TC50/EC50) above 1400. The compounds localized primarily in the lysosomes, leading to their rupture after light activation. This induced an apoptotic cell death pathway with secondary necrosis because of extensive and swift damage to the cells. This work demonstrates the importance of a bulky and rigid arrangement of peripheral substituents in the development of photosensitizers.

A phthalocyanine-based self-assembled nanophotosensitizer for efficient in vivo photodynamic anticancer therapy

To develop highly efficient photosensitizers for photodynamic therapy, herein a zinc(II) phthalocyanine-folate conjugate (PcN-FA) used to construct an activatable nanophotosensitizer (NanoPcN-FA) through a facile self-assembly. The self-assembled nanophotosensitizer (NanoPcN) without folate-modification was used as a negative control. After self-assembly, the photoactivities of NanoPcN-FA was quenched. The in vitro studies showed that NanoPcN-FA could be taken in by folate-receptor (FR)-positive SKOV3 cells and activated in the cells. It also exhibited slightly higher photocytotoxicity against SKOV3 cells than NanoPcN. Moreover, the competitive assay confirmed that the cellular uptake of NanoPcN-FA was through a FR-mediated process. Finally, the in vivo results indicated that NanoPcN-FA could target tumor tissue of S180 rat ascitic tumor-bearing mice due to the folic acid (FA) ligand, leading to a highly efficient antitumor photodynamic efficacy with the tumor inhibition rate of 95%.

A study on photophysical and photodynamic properties of donor–acceptor BODIPY complexes: Correlation between singlet oxygen quantum yield and singlet-triplet energy gap

Donor–acceptor (D–A) triplet photosensitizers have gained considerable attention in the field of photodynamic therapy. While numerous studies have been conducted on these photosensitizers, their energy transfer mechanism has not been completely elucidated. Herein, we prepared BODIPY-based D–A complexes (AM2–4) to investigate their photophysical and solvatochromic properties. In addition, the hypothesis that a decrease in the singlet and triplet energy gap (ΔEST) can increase the intersystem crossing rate and singlet oxygen quantum yield (SOQY) was investigated. Moreover, by designing the experiments under more controlled conditions than those reported in previous studies, we obtained more accurate data. AM2–4 materials with the charge-transfer (CT) character exhibited higher SOQY (0.32–0.44) than AM1 without the CT character. Besides, as the electron-accepting power of the photosensitizers increased, ΔEST between the first singlet excited state and triplet excited state decreased, resulting in an increased SOQY. This study elucidates the molecular mechanism of D–A triplet photosensitizers and contributes to the development of efficient photosensitizers for photodynamic therapy.

A non-aggregated silicon(IV) phthalocyanine-lactose conjugate for photodynamic therapy

To develop a highly efficient photosensitizer for photodynamic therapy (PDT), we have designed and synthesized a phthalocyanine-lactose conjugate (Pc-Lac) through axial modification of silicon(IV) phthalocyanine with lactose moieties. With the lactose substituents, Pc-Lac is highly hydrophilic and non-aggregated with efficient reactive oxygen species (ROS) generation in aqueous media. With these desirable properties, Pc-Lac shows high photocytotoxicity and cellular uptake toward HepG2 cells. In addition, in vivo fluorescence imaging shows that Pc-Lac could selectively remain at tumor site, leading to its enhanced photodynamic efficacy against H22 tumor-bearing mice. Therefore, Pc-Lac shows a great potential as a highly efficient molecular photosensitizer for PDT.

Covalent Organic Frameworks as Favorable Constructs for Photodynamic Therapy.

Covalent organic frameworks (COFs) with 2D π-conjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy. Two molecules, 5',5''''-(1,4-phenylene)bis(([1,1':3',1''-terphenyl]-4,4''-dicarbaldehyde)) (L-3C) and 4,4',4''-(1,4-phenylene)bis(([2,2':6',2''-terpyridine]-5,5''-dicarbaldehyde)) (L-3N), inactive to generating reactive oxygen species (ROS), were linked to form two COFs, COF-808 and COF-909, respectively, exhibiting excellent ROS production efficiency. The high permanent porosity of these COFs (surface areas 2270 and 2610 m2 g-1 ) promoted diffusion of both oxygen and release of ROS in cells. This, combined with the excellent photostability and biocompatibility, led to excellent PDT performance. In vitro, over 80 % of tumor cells were killed after PDT treatment using COF-909 at the concentration of 50 μg mL-1 for 150 s. In vivo, drastic reduction of tumor size was observed (from 9 mm to less than 1 mm) after 10 day treatment.