Photosensitizers For Photodynamic Therapy Research Articles

Mitochondria Targeted AIE Probes for Cancer Phototherapy.

In recent years, mitochondrion (powerhouse of the cells) gained lots of interest as one of the unorthodox targets for futuristic cancer therapy. As a result, novel small molecules were developed to damage and image mitochondria in cancer models. In this context, aggregation-induced emission probes (AIEgens) received immense attention due to their applications in mitochondria-targeted biosensing, imaging, and biomedical theranostics. On the other hand, phototherapy (photodynamic and photothermal) has emerged as a powerful alternative to manage cancer due to its less invasive nature. However, merging these two areas to engineer mitochondria-targeted phototherapeutic probes for cancer diagnosis and treatment has remained a major challenge. In this mini-review, we will outline the development of novel mitochondria-targeted small molecule AIEgens as imaging agents and photosensitizers for photodynamic therapy along with dual photodymanic-phototheramal therapy and chemo-photodynamic therapy. We will also highlight the current challenges in developing mitochondria-targeted photothermal therapy probes for future biomedical theranostic applications to manage cancer.

Fullerenes (C60, C70) as Photosensitizers for PDT

Fullerenes (C60, C70) as Photosensitizers for PDT

Towards Selective Delivery of Novel Metal-Based Photosensitizers for Anticancer Photodynamic Therapy

Towards Selective Delivery of Novel Metal-Based Photosensitizers for Anticancer Photodynamic Therapy

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.

Pentacene Nanorods as Effective Photosensitizer for Photodynamic Therapy of Tumor via Singlet Fission

AbstractSinglet fission (SF), whereby a singlet exciton is converted into a pair of triplet excitons, can improve the efficiency of solar cells. Pentacene has been extensively studied as the most promising SF compound, owing to its 200% yield of triplet states. However, the easy degradation of pentacene in the presence of light and air owing to photooxidation cannot be explained by the classical 1O2 generation mechanism. To address this issue, in the present study, pentacene nanorods (Pc NRs) are prepared as a novel photosensitizer (PS); self‐carried Pc NRs exhibited higher 1O2 generation capacity. Thus, a novel 1O2 generation mechanism is proposed based on the SF effect. The initial photon absorption occurs to access single‐exciton states, S1–S3. Excited‐state Pc pairs accelerate the SF effect in pentacene NRs, leading to a non‐adiabatic transition to the dark D state. Dark D state is a singlet state by two triplets coupled overall, and it can transfer its energy to 3O2 for generating 1O2. Using Pc NRs as PSs, photodynamic therapy (PDT) inhibits tumor growth in 4T1 tumor‐bearing mice upon 405‐nm‐wavelength and 650‐nm‐wavelength laser irradiations. This study paves the way to discover novel PSs that are not considered with classical 1O2 generation mechanisms.

Solvent Induced Conversion of a Self-Assembled Gyrobifastigium to a Barrel and Encapsulation of Zinc-Phthalocyanine within the Barrel for Enhanced Photodynamic Therapy.

A rare gyrobifastigium architecture (GB) was constructed by self-assembly of a tetradentate donor (L) with PdII acceptor in DMSO. The GB was converted to its isomeric tetragonal barrel (MB) upon treatment with water. The hydrophobic cavity of MB has been explored for the encapsulation of zinc-phthalocyanine (ZnPc), which is an excellent photosensitizer for photodynamic therapy (PDT). However, the poor water-solubility and aggregation tendency are the main reasons for the suboptimal PDT performance of free ZnPc in the aqueous medium. Effective solubilization of ZnPc in an aqueous medium was achieved by encapsulating it in the cavity of MB. The inclusion complex (ZnPc⊂MB) showed enhanced singlet oxygen generation in water. Higher cellular uptake and anticancer activity of the ZnPc⊂MB compared to free ZnPc on HeLa cells indicate that encapsulation of ZnPc in an aqueous host is a potential strategy for enhancement of its PDT activity in water.

Solvent Induced Conversion of a Self‐Assembled Gyrobifastigium to a Barrel and Encapsulation of Zinc‐Phthalocyanine within the Barrel for Enhanced Photodynamic Therapy

AbstractA rare gyrobifastigium architecture (GB) was constructed by self‐assembly of a tetradentate donor (L) with PdII acceptor in DMSO. The GB was converted to its isomeric tetragonal barrel (MB) upon treatment with water. The hydrophobic cavity of MB has been explored for the encapsulation of zinc‐phthalocyanine (ZnPc), which is an excellent photosensitizer for photodynamic therapy (PDT). However, the poor water‐solubility and aggregation tendency are the main reasons for the suboptimal PDT performance of free ZnPc in the aqueous medium. Effective solubilization of ZnPc in an aqueous medium was achieved by encapsulating it in the cavity of MB. The inclusion complex (ZnPc⊂MB) showed enhanced singlet oxygen generation in water. Higher cellular uptake and anticancer activity of the ZnPc⊂MB compared to free ZnPc on HeLa cells indicate that encapsulation of ZnPc in an aqueous host is a potential strategy for enhancement of its PDT activity in water.

Genetic deviation associated with photodynamic therapy in HeLa cell

Photodynamic therapy (PDT) is a method that is used in cancer treatment. The main therapeutic effect is the production of singlet oxygen (1O2). Phthalocyanines for PDT produce high singlet oxygen with absorbers of about 600–700 nm. AimIt is aimed to analyze cancer cell pathways by flow cytometry analysis and cancer-related genes with q-PCR device by applying phthalocyanine L1ZnPC, which we use as photosensitizer in photodynamic therapy, in HELA cell line. In this study, we investigate the molecular basis of L1ZnPC's anti-cancer activity. Material methodThe cytotoxic effects of L1ZnPC, a phthalocyanine obtained from our previous study, in HELA cells were evaluated and it was determined that it led to a high rate of death as a result. The result of photodynamic therapy was analyzed using q-PCR. From the data received at the conclusion of this investigation, gene expression values were calculated, and expression levels were assessed using the 2−∆∆Ct method to examine the relative changes in these values. Cell death pathways were interpreted with the FLOW cytometer device. One-Way Analysis of Variance (ANOVA) and the Tukey-Kramer Multiple Comparison Test with Post-hoc Test were used for the statistical analysis. ConclusionIn our study, it was observed that HELA cancer cells underwent apoptosis at a rate of 80% with drug application plus photodynamic therapy by flow cytometry method. According to q-PCR results, CT values ​​of eight out of eighty-four genes were found to be significant and their association with cancer was evaluated. L1ZnPC is a new phthalocyanine used in this study and our findings should be supported by further studies. For this reason, different analyses are needed to be performed with this drug in different cancer cell lines. In conclusion, according to our results, this drug looks promising but still needs to be analyzed through new studies. It is necessary to examine in detail which signaling pathways they use and their mechanism of action. For this, additional experiments are required.

AIEgens/Mitochondria Nanohybrids as Bioactive Microwave Sensitizers for Non-Thermal Microwave Cancer Therapy.

Aggregation-induced emission luminogens (AIEgens) are widely used as photosensitizers for image-guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep-seated tumors by visible-light-sensitized aggregation-induced emission(AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial-targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep-seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.

Polymer photosensitizing systems containing porphyrins, dinitrosyl iron complexes, and sodium alginate in the generation of singlet oxygen

The activity of photosensitizing systems based on water-soluble photoditazine (PDZ) and hydrophobic fluorinated tetraphenylporphyrin (TPPF20) solubilized polyvinylpyrrolidone (PVP) (in the case PDZ) and pluronic F127 (in the case TPPF20) was studied in a model reaction of tryptophan (Trp) photooxidation. We also studied the effect of dinitrosyl iron complex (DNIC) and sodium alginate (SA) polysaccharide on the photosensitizing activity of both PDZ in the presence of PVP and TPPF20 solubilized with pluronic F127 in a model reaction of Trp photooxidation. It was shown that TPPF20 solubilized with pluronic F127 exhibits high photocatalytic activity in the presence of both DNIC and SA. It was also shown that PVP is able to prevent the damaging effect exerted by active NO radicals produced during the photodecomposition of DNIC on PDZ molecules. Moreover, it was demonstrated that SA does not influence the photocatalytic activity of PDZ in the presence and absence of PVP. Using the dynamic light scattering method, it was found that SA macromolecules in the presence of PVP are capable of self-association, which, due to the ‘excluded volume’ effect, can cause a slight increase in the rate of photocatalytic reaction. The effectiveness of using PDZ in combination with PVP in the presence of SA and DNIC as a photosensitizer in antimicrobial photodynamic therapy was studied via in vivo experiments on a model of a full-layer planar wound in laboratory rats. Morphological studies have shown that under photodynamic action on wounds, the use of these systems (compared to photoexcitation of an aqueous solution of the initial PDZ) stimulates the transition of the inflammatory phase to the reparative (proliferative) phase. In addition, the process of cleansing wounds from microflora and devitalized tissues is accelerated, the disturbed microcirculation is restored, the proliferation of fibroblasts and blood vessels, and collagen synthesis are accelerated. It is suggested that the PDZ-PVP-SA-DNIC systems can be used in PDT procedures for the treatment of inflammatory diseases of the skin and soft tissues.

Theoretical study of C6F5-corrole molecules functionalized with aromatic groups for Photodynamic Therapy

The singlet oxygen generation by electronically excited molecules in photodynamic therapy (PDT) requires light absorption within a specific wavelength window, and a subsequent intersystem crossing transition to a triplet excited state that is, at least, 0.98 eV higher in energy than the singlet ground state. Tetrapyrrolic macrocycles, such as porphyrin and corrole, have been widely used in oxygen singlet generation for PDT. Suitable functionalization can potentialize these macrocycles as photosensitizers. In this contribution, we use Density Functional Theory (DFT) calculations to determine the structural, electronic and spectroscopic properties of corrole macrocycles bound to different polycyclic aromatic groups in the gas phase, dichloromethane, and water. We also calculate the spin–orbit coupling (SOC) matrix elements of the intersystem crossing channels involving the first excited singlet states and excited triplet states. The results for optical absorption show that the threshold wavelength for optical absorption increases with the polarity of the environment and the number of aromatic rings of the ligands, whereas the oscillator strengths increase with the polarity of the environment but decrease with the number of aromatic rings. It is verified that the triplet excited states involved in the intersystem crossing transitions satisfy the energy requirement for the oxygen singlet generation. The magnitude of spin–orbit coupling (SOC) matrix elements associated with the intersystem crossing are also seen to be dependent on the environment involving the corrole molecules, and on the number of aromatic rings of the ligands connected to the corrole. Further, the binding of the functionalized corrole molecules with biomolecules as the calf thymus DNA and human serum albumin is studied and characterized through molecular docking. These results show that the corrole macrocycles, suitably functionalized with polycyclic aromatic groups, fulfill several criteria to be considered as good PDT photosensitizers.

Curcumin a Natural Phenol and Its Therapeutic Role in Cancer and Photodynamic Therapy: A Review

Cancer continues to cause an alarming number of deaths globally, and its burden on the health system is significant. Though different conventional therapeutic procedures are exploited for cancer treatment, the prevalence and death rates remain elevated. These, therefore, insinuate that novel and more efficient treatment procedures are needed for cancer. Curcumin, a bioactive, natural, phenolic compound isolated from the rhizome of the herbaceous plant turmeric, is receiving great interest for its exciting and broad pharmacological properties. Curcumin presents anticancer therapeutic capacities and can be utilized as a photosensitizing drug in cancer photodynamic therapy (PDT). Nonetheless, curcumin's poor bioavailability and related pharmacokinetics limit its clinical utility in cancer treatment. This review looks at the physical and chemical properties, bioavailability, and safety of curcumin, while focusing on curcumin as an agent in cancer therapy and as a photosensitizer in cancer PDT. The possible mechanisms and cellular targets of curcumin in cancer therapy and PDT are highlighted. Furthermore, recent improvements in curcumin's bioavailability in cancer therapy using nanoformulations and delivery systems are presented.

Engineering Multifunctional Thylakoid as an Oxygen Self-Supplying Photosensitizer for Esophageal Squamous Cell Carcinoma-Targeted Photodynamic Therapy

Open AccessCCS ChemistryRESEARCH ARTICLES19 Dec 2022Engineering multifunctional thylakoid as an oxygen self-suppling photosensitizer for esophageal squamous cell carcinoma-targeted photodynamic therapy Yingqiu Qi, Hui Wang, Anni Du, Chen Liu, Xiaofan Sun, Xiaocao Meng, Jinxiu Shen, Sai-Yang Zhang, Li-Rong Zhang, Bing Jiang, Guangjun Nie and Huan Min Yingqiu Qi Google Scholar More articles by this author , Hui Wang Google Scholar More articles by this author , Anni Du Google Scholar More articles by this author , Chen Liu Google Scholar More articles by this author , Xiaofan Sun Google Scholar More articles by this author , Xiaocao Meng Google Scholar More articles by this author , Jinxiu Shen Google Scholar More articles by this author , Sai-Yang Zhang Google Scholar More articles by this author , Li-Rong Zhang Google Scholar More articles by this author , Bing Jiang Google Scholar More articles by this author , Guangjun Nie Google Scholar More articles by this author and Huan Min Google Scholar More articles by this author https://doi.org/10.31635/ccschem.022.202202404 SectionsSupplemental MaterialAboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Photodynamic therapy (PDT) has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma (ESCC). However, the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery, insufficient oxygen supply and neutralization by excessive glutathione (GSH) in tumor tissue. Herein, an engineered multifunctional thylakoid nanostructure, [email protected]@GA (abbreviated as TEPG), composed of a thylakoid membrane (TM) and ESCC cell membrane (EM)-fused biomembrane shell (TM-EM) and gambogic acid (GA)-loaded poly (lactic-co-glycolic acid) nanocore, was designed for enhanced PDT for ESCC. When fused with EM, TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage. The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue. Moreover, when TEPG was selectively internalized by ESCC cells, GA was released to consume the excessive intracellular GSH. Under infrared irradiation, the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG. An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation. This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC. Download figure Download PowerPoint Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentNot Yet AssignedSupporting Information Copyright & Permissions© 2022 Chinese Chemical Society Downloaded 50 times PDF downloadLoading ...

Improving antimicrobial activity against endodontic biofilm after exposure to blue light-activated novel curcumin nanoparticle

New therapies involving natural products and nanobiotechnology open additional perspectives to reduce endodontic infections. Curcumin is a natural polyphenol extracted from the dry rhizome of curcuma long Linn with therapeutic properties for application in nanobiotechnology and as a photosensitizer for photodynamic therapy. This study aimed to synthesize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with curcumin (NP+Cur), and evaluate its antimicrobial activity against endodontic biofilms. Additionally, its biocompatibility using oral keratinocytes was assessed. The polymeric NP+Cur was prepared by the nanoprecipitation method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were calculated for the three endodontic bacteria (Enterococcus faecalis, Streptococcus oralis and Actinomyces viscosus). Antibacterial activity of NP+Cur against single- and multispecies biofilm pre-formed on the botton 24-well plate and into dentin tubules of bovine teeth were evaluated by colony forming units and confocal laser scanning microscopy. The pre-irradiation time was 5 min followed by exposure to blue light-emitting diode at 450 nm for the photodynamic treatment. Cell viability using oral keratinocytes was assessed by Alamar Blue assay. MIC and MBC showed antibacterial activity of NP+Cur against endodontic bacteria. A treatment of pre-formed biofilms of endodontic bacteria with NP+Cur also significantly decreased bacterial viability. The concentration of 325 μg/mL of photoactivated NP+Cur was the one that most reduced the viability of the endodontic bacteria evaluated. Regarding biocompatibility, NP+Cur 325 μg/mL and pure nanoparticles showed a cell viability greater than 80%. The novel polymeric nanoparticles loaded with curcumin may be a promising adjunct use to treatment of endodontic infections.

Molecular engineering to construct thieno[3,2-c]pyridinium based photosensitizers for mitochondrial polarity imaging and photodynamic anticancer therapy

Mitochondria are indispensable organelles and have become attractive targets for a lot of diseases. More and more mitochondria targeting photosensitizers (PSs) have been developed for disease diagnosis and photodynamic anticancer therapy. However, current PSs encountered significant limitations, such as short excitation/emission wavelength, low quantum yield (QY), insufficient reactive oxygen species (ROS) generation efficiency. In this study, a series of novel thieno[3,2-c]pyridinium based near-infrared (NIR) aggregation-induced emission PSs (AIE PSs) for targeting mitochondria was rational designed and synthesized by regulating the molecular engineering of D-π-A structure. The synergistic effect of strong D and extended π system fabricated a progressively strong intramolecular charge transfer (ICT) effect to accelerate intersystem crossing (ISC) of excited electrons, which were favorable for the LIQ-TPA-DTZ with NIR emission, good AIE performance, high QY, and high 1O2 and •OH generation efficiency. LIQ-TPA-DTZ can sensitively detect the mitochondrial polarity changes in living cells. Furthermore, it could trigger the mitochondria apoptosis pathway to efficiently photodynamic kill cancer cells and restrain tumor growth in vivo. This work not only provides a powerful tool for mitochondrial targeting imaging and cancer therapy but also offers a facile strategy for constructing thieno[3,2-c] pyridinium based AIE PSs.

Phthalocyanine photosensitizers with bathochromic shift, of suitable brightness, capable of producing singlet oxygen with effective efficiency

• New phthalocyanine derivatives as photosensitizers were designed and synthesized. • The phthalocyanines dissolve well in common solvents without aggregation. • The phthalocyanines have improved fluorescence and optical absorption properties. • The phthalocyanines have improved photochemical properties and photostability. • The phthalocyanines can be used as photosensitizers in photocatalytic applications. In this study, novel 3-(2,3-dimethoxyphenoxy)phthalonitrile 2 and its non-peripheral tetra-2,3-dimethoxyphenoxy substituted metal-free phthalocyanine 3 compounds were synthesized. Then, the magnesium(II), zinc(II), and indium(III) acetate phthalocyanine complex derivatives ( 4-6 ) of compound 3 were synthesized using the corresponding metal salts by the template effect. The structures of novel phthalonitrile derivative 2 and its metal-free phthalocyanine compounds 3 as well as different metal-containing phthalocyanine complexes ( 4-6 ) were characterized by elemental analysis, FTIR, UV-vis, 1 H NMR, and MALDI-TOF mass spectroscopic techniques. The phthalocyanines ( 3-6 ) can dissolve well in different polar protic, polar aprotic, and non-polar solvent types without aggregation, with maximum absorption intensity and bathochromic effect. Photophysicochemical properties of the phthalocyanines ( 3-6 ) in dimethyl sulfoxide and important spectral parameter values such as molar extinction coefficient, oscillator strength, and electrical dipole strength were determined, and they were also compared with each other and with their unsubstituted counterparts. It was determined that the phthalocyanines ( 3-6 ) have suitable and sufficient fluorescence quantum yields, fluorescence lifetimes, fluorescence brightness, and other photophysical properties, as well as singlet oxygen generation, phototoxic power, and photostability properties. The phthalocyanines ( 3-6 ), particularly zinc(II) and indium(III) acetate phthalocyanines have remarkable potential for use as Type II photosensitizers for cancer therapy in photodynamic therapy. The phthalocyanines ( 3-6 ) may be promising candidates for various applications as photosensitizers for photodynamic therapy, especially in combination with fluorescent imaging.

Upconversion nanoparticle-based optogenetic nanosystem for photodynamic therapy and cascade gene therapy.

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.

Translational albumin nanocarrier caging photosensitizer for efficient cancer photodynamic therapy.

It still remains a great challenge to efficiently treat malignant cancers which severely threaten human health. Photodynamic therapy (PDT) as a localized therapeutic modality has improved the therapeutic efficacy via chemical damage through reactive oxygen species (ROS). However, their efficacy is severely hampered by insufficient targeted delivery of photosensitizers owing to the lack of suitable carrier with facile preparation process and the clinical applicability. Herein, we applied clinically approved human serum albumin as the nanoreactor to encapsulate photosensitizers Chlorin e6 (Ce6) for enhancing their tumor accumulation and subsequently potent PDT effect against bladder cancer models. Albumin-loaded Chlorin e6 nanoparticles (CA-NPs) with rational nanoscale size exhibit increased reactive oxygen species production and excellent resistance to photobleaching. Moreover, CA-NPs could be efficiently internalized by tumor cells and locate in the lysosome, while they rapidly translocate to cytosol after irradiation to induce remarkable cytotoxicity (IC50 ∼5.8μg/ml). Furthermore, CA-NPs accumulate effectively in tumor tissue to afford total eradication of murine bladder tumor after single injection. More importantly, we also evidence the superior PDT effect in fresh human bladder tumor tissues via abundant reactive oxygen species generation and subsequent cell apoptosis. These findings demonstrate that human serum albumin acts as a universal tool to load small organic photoactivatable molecule with remarkable effectiveness and readiness for clinical translation.

Acidification of blue photosensitizers for antimicrobial photodynamic therapy impairs photodynamic reaction.

Introduction: Antimicrobial photodynamic therapy (aPDT) is an adjuvant treatment for periodontal disease. Methylene blue (MB) and toluidine blue O (TBO) are commonly used as photosensitizers in aPDT. However, the pH of blue dyes is a rarely discussed topic. Objectives: The aim of this study was to evaluate dentin demineralization and optical properties of acidified (pH1) MB and TBO. A secondary objective of this paper was to discuss the regular pH of blue photosensitizers and their clinical applications. Materials and Methods: Acid TBO and MB (pH1) were compared to conventional dyes and/or treatments. Dentin demineralization was measured by profilometry and microhardness test. Optical properties were evaluated by absorbance measurements and photodegradation rate. Statistical analyses were performed with Kruskal-Wallis test (p<0.05). Results: Acid TBO promoted dentin demineralization like positive control (citric acid/tetracycline) (p>0.05). Acidification of MB and TBO promoted no photodegradation and change of absorption band, respectively. Acid MB and TBO promoted similar demineralization of dentin surfaces as citric acid/tetracycline. Conclusion: Acidification impaired a photodynamic reaction, impeding the use of acidified photosensitizers in aPDT procedures.

Development of a new minimally invasive phototherapy for lung cancer using antibody-toxin conjugate.

Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and laser irradiation. The effectiveness of current PDT using red light for advanced cancers is limited, because red light can only reach depths within a few millimeters. To enhance the antitumor effect for lung cancers, we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin and a PS, mono-L-aspartyl chlorin e6 (NPe6). We examined whether cetuximab encapsulated in endosomes was released into the cytosol by PS in PDT under light irradiation. A431 cells were treated with fluorescein isothiocyanate-labeled cetuximab, NPe6, and light irradiation and were observed with fluorescence microscopy. We analyzed the cytotoxicity of saporin-conjugated cetuximab (IT-cetuximab) in A431, A549, and MCF7 cells and the antitumor effect in model A549-bearing mice in vivo using the iTAP method. Fluorescent microscopy analysis showed that the photodynamic effect of NPe6 (20 μM) and light irradiation (37.6J/cm2 ) caused the release of cetuximab from the endosome into the cytosol. In vitro analysis demonstrated that the iTAP method enhanced the cytotoxicity of IT-cetuximab by the photodynamic effect. In in vivo experiments, compared with IT-cetuximab alone or PDT alone, the iTAP method using a low dose of IT-cetuximab showed the greatest enhancement of the antitumor effect. Our study is the first report of the iTAP method using NPe6 for lung cancer cells. The iTAP method may become a new, minimally invasive treatment superior to current PDT methods.