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Photodynamic therapy (PDT) has shown promise as a modality for the treatment of cervical cancer caused by the human papillomavirus (HPV). This review provides a comprehensive examination of the role of PDT in overcoming the challenges presented by conventional treatments for cervical cancer. Beginning with an overview of the relationship between cervical cancer and HPV infection, the review introduces the principles of PDT, its mechanism of action, and its potential as an innovative treatment strategy. The review highlights preclinical studies in animal models that demonstrate the efficacy of PDT in targeting HPV-infected cervical cells and provide mechanistic insights into its cytotoxic effects. We reviewed clinical studies and case reports highlighting the potential of PDT as an alternative or adjunctive treatment option. Challenges and limitations, including depth of light penetration, photosensitizer specificity, and standardization of protocols, will be discussed in the context of potential side effects and comparison with conventional treatments. Future directions include ongoing research, combination therapies with immunotherapy or targeted agents, advances in photosensitizer development, and personalized approaches. The advancement of PDT promises to change the landscape of HPV-associated cervical cancer treatment by providing a targeted, personalized, and minimally invasive approach.

Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT's efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT's dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT's principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin (IT) and a PS for PDT and light irradiation. In our prior study, we demonstrated that an immunotoxin (IT) consisting of an anti-ROBO1 antibody conjugated to saporin, when used in combination with the photosensitizer (PS) disulfonated aluminum phthalocyanine (AlPcS2a) and irradiated with light at the appropriate wavelength, resulted in increased cytotoxicity against head and neck squamous cell carcinoma (HNSCC) cells. ROBO1 is a receptor known to be involved in the progression of cancer. In this study, we newly investigate the iTAP targeting epidermal growth factor receptor (EGFR) which is widely used as a therapeutic target for HNSCC. Methods: We checked the expression of EGFR in HNSCC cell lines, SAS, HO-1-u-1, Sa3, and HSQ-89. We analyzed the cytotoxicity of saporin-conjugated anti-EGFR antibody (cetuximab) (IT-Cmab), mono-L-aspartyl chlorin e6 (NPe6, talaporfin sodium), and light (664 nm) irradiation (i.e., iTAP) in SAS, HO-1-u-1, Sa3, and HSQ-89 cells. Results: EGFR was expressed highly in Sa3, moderately in HO-1-u-1, SAS, and nearly not in HSQ-89. Cmab alone or IT-Cmab alone did not show cytotoxic effects in Sa3, HO-1-u-1, and HSQ-89 cells, which have moderate or low expression levels of EGFR protein. However, the iTAP method enhanced the cytotoxicity of IT-Cmab by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression. Conclusion: Our study is the first to report on the iTAP method using IT-Cmab and NPe6 for HNSCC. The cytotoxic effects are enhanced in cell lines with moderate levels of EGFR protein expression, but not in nonexpressing cell lines, which is expected to expand the range of therapeutic windows and potentially reduce complications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis(N-alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N-alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms (Zn-C8). [ABSTRACT FROM AUTHOR]

Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT’s efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT’s dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT’s principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies.

[Display omitted] The two-step synthesis of porphyrin derivatives, exhaustively bbb-substituted at the 'Eastern half', starting from meso- tetraarylporphyrin chelates (Cuii, Znii, Niii) upon their reaction with nitric acid, is described. The intermediates obtained (mainly dinitro-derivatives) in the reaction with carbanions bearing a leaving group X at the reactive centre give tetrasubstituted at the bbb-positions products, the ones of vicarious nucleophilic substitution of hydrogen. The products seem to be potential anticancer PDT agents, practically unavailable by other methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses photoreactive agents and light irradiation, while photodynamic therapy (PDT) is an existing phototherapy using photosensitizers and light irradiation as well as NIR-PIT. The current study investigated the properties of these therapies and their differences with a focus on their cellular binding/uptake specificity and cytotoxicity in vitro. NIR-PIT showed molecule-selective responses and cytotoxicity, whereas PDT showed non-selective cell type responses and cytotoxicity. Additionally, NIR-PIT and PDT induced damage-associated molecular patterns (DAMPs), a surrogate marker of immunogenic cell death, although PDT had different sensitivity between cell lines. Therefore, molecule-specific NIR-PIT may have advantages compared with PDT in terms of efficiency in tumor visualization and induction of DAMPs. Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In the present study, we compared these therapies in vitro. The characterization of cellular binding/uptake specificity and cytotoxicity were examined using two mAb-IR700 forms and a conventional PDT agent, talaporfin sodium, in three cell lines. As designed, mAb-IR700 had high molecular selectivity and visualized target molecule-positive cells at the lowest concentration examined. NIR-PIT induced necrosis and damage-associated molecular patterns (DAMPs), a surrogate maker of immunogenic cell death. In contrast, talaporfin sodium was taken up by cells regardless of cell type, and its uptake was enhanced in a concentration-dependent manner. PDT induced cell death, with the pattern of cell death shifting from apoptosis to necrosis depending on the concentration of the photosensitizer. Induction of DAMPs was observed at the highest concentration, but their sensitivity differed among cell lines. Overall, our data suggest that molecule-specific NIR-PIT may have potential advantages compared with PDT in terms of the efficiency of tumor visualization and induction of DAMPs. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid synthesized in all nucleated mammalian cells. As a porphyrin precursor, ALA is metabolized in the heme biosynthetic pathway to produce protoporphyrin IX (PpIX), a fluorophore and photosensitizing agent. ALA administered exogenously bypasses the rate-limit step in the pathway, resulting in PpIX accumulation in tumor tissues. Such tumor-selective PpIX disposition following ALA administration has been exploited for tumor fluorescence diagnosis and photodynamic therapy (PDT) with much success. Five ALA-based drugs have now received worldwide approval and are being used for managing very common human (pre)cancerous diseases such as actinic keratosis and basal cell carcinoma or guiding the surgery of bladder cancer and high-grade gliomas, making it the most successful drug discovery and development endeavor in PDT and photodiagnosis. The potential of ALA-induced PpIX as a fluorescent theranostic agent is, however, yet to be fully fulfilled. In this review, we would like to describe the heme biosynthesis pathway in which PpIX is produced from ALA and its derivatives, summarize current clinical applications of ALA-based drugs, and discuss strategies for enhancing ALA-induced PpIX fluorescence and PDT response. Our goal is two-fold: to highlight the successes of ALA-based drugs in clinical practice, and to stimulate the multidisciplinary collaboration that has brought the current success and will continue to usher in more landmark advances. [ABSTRACT FROM AUTHOR]

The most prevalent type of gynecological malignancy globally is cervical cancer (CC). Complicated by tumor resistance and metastasis, it remains the leading cause of cancer deaths in women in South Africa. Early CC is managed by hysterectomy, chemotherapy, radiation, and more recently, immunotherapy. Although these treatments provide clinical benefits, many patients experience adverse effects and secondary CC spread. To minimize this, novel and innovative treatment methods need to be investigated. Photodynamic therapy (PDT) is an advantageous treatment modality that is non-invasive, with limited side effects. The Cannabis sativa L. plant isolate, cannabidiol (CBD), has anti-cancer effects, which inhibit tumor growth and spread. This study investigated the cytotoxic combinative effect of PDT and CBD on CC HeLa cells. The effects were assessed by exposing in vitro HeLa CC-cultured cells to varying doses of ZnPcS4 photosensitizer (PS) PDT and CBD, with a fluency of 10 J/cm2 and 673 nm irradiation. HeLa CC cells, which received the predetermined lowest dose concentrations (ICD50) of 0.125 µM ZnPcS4 PS plus 0.5 µM CBD to yield 50% cytotoxicity post-laser irradiation, reported highly significant and advantageous forms of cell death. Flow cytometry cell death pathway quantitative analysis showed that only 13% of HeLa cells were found to be viable, 7% were in early apoptosis and 64% were in late favorable forms of apoptotic cell death, with a minor 16% of necrosis post-PDT. Findings suggest that this combined treatment approach can possibly induce primary cellular destruction, as well as limit CC metastatic spread, and so warrants further investigation. [ABSTRACT FROM AUTHOR]

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular "Trojan horses" in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC. [ABSTRACT FROM AUTHOR]

Immunogenic proteins in cancer are relevant targets for drug delivery. In Photodynamic Therapy (PDT), surface antigens have previously been used to deliver the photosensitizer (PS) to the tumor microenvironment for specific targeting. However, can we target intracellular antigens to achieve more than surface recognition? Can we possibly increase PS intracellular localization and prevent drug efflux at the same time? In this study, these questions were addressed by using a compound that can not only specifically recognize and bind to intracellular E6 oncoproteins in Human Papillomavirus (HPV)-Transformed cancer cells, but is also capable of enhancing transmembrane uptake using the cells' own active transport mechanisms. HPV-transformed SiHa cells were cultured in vitro, and the resistant subpopulation was isolated using Magnetic Activated Cell Sorting (MACS). PDT was performed on four different cell types with varying physiognomies in terms of HPV oncoprotein expression and physiological form. Results demonstrated that tagging PSs on a carrier molecule that specifically delivers the PS inside the cells that express the target proteins enhanced both cellular uptake and retention of the PS even in the presence of drug efflux proteins on resistant subpopulations. These findings provide insight into the possibility of preventing cell-mediated resistance to PDT. [ABSTRACT FROM AUTHOR]

Many disorders, both cancerous and non-cancerous, may be effectively treated using photodynamic therapy. In this scenario, photosensitizer drugs are first excited by light of the appropriate wavelength (in the visible-NIR range), after which they transmit their extra energy to molecular oxygen, resulting in the creation of strongly cytotoxic singlet oxygen. Indium oxide nanoparticles are optically transparent materials and can be used to incorporate fluorophores and photosensitizer drugs. Herein, we report the use of indium oxide nanoparticles incorporated with a photosensitizer. These nanoparticles have been synthesized in a methanolic medium. The characterization of prepared nanoparticles included FTIR, XRD, TEM, and optical studies (UV-visible and fluorescence spectroscopy). Cell viability studies demonstrated that the photosensitizer-incorporated nanoparticles showed cytotoxic effects only upon light irradiation. The results indicate the promise of photosensitizer-incorporated indium oxide nanoparticles as delivery agents in photodynamic therapy. [ABSTRACT FROM AUTHOR]

Phototherapy, which mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), is a new type of tumor therapy that uses a specific light source to irradiate enriched phototherapy drugs at the tumor site and produce reactive oxygen species or induce a photothermal action to kill the tumor. Human serum albumin (HSA)—the most abundant carrier protein in serum—has diverse binding domains; thus, it can be used as a carrier to bind various photosensitizers and photothermal converting agents (PTCAs) to improve the therapeutic efficacy of PDT and PTT. Compared to traditional tumor therapy, phototherapy administered via HSA delivery has the advantages of strong targeting and less trauma and has been widely studied to date. However, this interesting topic has not yet been systematically reviewed. Herein, we focus on the recent research progress on photosensitizers and PTCAs in HSA-delivered PDT and PTT, including their design and synthesis, tumor-targeting mechanisms, and tumor therapeutic applications. Furthermore, as clinical tumor treatment methods, PDT and PTT still have several drawbacks and limitations, such as the inability to spread to metastatic tumors, the dependence on the dose of photosensitizers and PTCAs, low light tissue penetration, and the requirement to avoid light for patients during treatment. This important review may facilitate the development of enhanced photosensitizers and PTCAs to provide highly powerful research tools for basic medical studies aimed at improving the diagnosis and treatment of clinical cancer. The recent developments of photosensitizers and photothermal converting agents (PTCAs) in HSA -delivered PDT, PTT, and PDT/PTT synergies have been reviewed for the first time. [Display omitted] • Significance of designing photosensitizers and photothermal converting agents (PTCAs) for human serum albumin (HSA)-delivered PDT and PTT. • Design strategies and mechanisms of photosensitizers and PTCAs used in PDT and PTT. • Advantages and limitations of photosensitizers and PTCAs in PDT and PTT. • Perspectives on photosensitizers and PTCAs in phototherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Ga(OH)PcOC, which is required for the use in PDT is stable under irradiation. • The Ga(OH)PcOC exhibited a strong red fluorescence at 714 nm. • The Ga(OH)PcOC is a good photosensitizer against Me45 cells, with low toxicity against normal HaCaT and NHDF cells. • The photosensitizer acts as a selective and active particle predominantly in cancer cells, less so in healthy cells. • PDT makes the cancers more sensitive to oxidation and apoptosis after photosensitizer accumulation and irradiation. Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn2+, Al3+, or Ga3+. Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • Coumarin-based poly(2-oxazoline)s copolymers self-assembled into nanovectors. • Coumarin function adds a synergistic phototoxic property to the self-assemblies. • Absence of a corona protein ensures the stealthy nature of these nanocarriers. Because of the difficult challenges of nanopharmaceutics, the development of a variety of nanovectors is still highly desired. Photodynamic therapy, which uses a photosensitizer to locally produce reactive oxygen species to kill the undesired cells, is a typical example for which encapsulation has been shown to be beneficial. The present work describes the use of coumarin-functionalized polymeric nanovectors based on the self-assembly of amphiphilic poly(2-oxazoline)s. Encapsulation of pheophorbide a, a known PDT photosensitizer, is shown to lead to an increased efficiency compared to the un-encapsulated version. Interestingly, the presence of coumarin both enhances the desired photocytotoxicity and enables the crosslinking of the vectors. Various nanovectors are examined, differing by their size, shape and hydrophilicity. Their behaviour in PDT protocols on HCT-116 cells monolayers is described, the influence of their crosslinking commented. Furthermore, the formation of a protein corona is assessed. [ABSTRACT FROM AUTHOR]

Introduction: Photodynamic therapy (PDT) is a demonstrated therapeutic method for basal cell carcinoma (BCC), which is the most common human cancer. Here, we present a case report about systemic PDT with chlorine e6 as a photosensitizer (PS) for BCC treatment. Case Report: A 78-year-old man was diagnosed with a history of a 4-year nodular BCC in the nasal area. The patient was under control and treatment for hypertension and type 2 diabetes. Chlorine e6 was injected intravenously at a 0.08 mg/kg dosage in 500 cc normal saline within 20 minutes. Three hours after injection, laser irradiation was performed with a wavelength of 665 nm, a dosage of 150 J/cm2, and an irradiance value of 150 mW/cm2. His nodular BCC was completely cured without any side effects after one session of PDT with chlorine e6. Conclusion: Systemic PDT with chlorine e6 as a PS may be safe and effective in removing BCC lesions due to the data obtained in a two-month follow-up. [ABSTRACT FROM AUTHOR]

• The main penetration of the photosensitizer THPTS into the skin occurs up to 10 min incubation time. • A penetration time >10 min promotes the loss of functionality of THPTS. • An irradiation between 400 and 700 nm is needed to activate THPTS in order to develop its effect as photosensitizer. • During PDT treatment mainly reactive oxygen species (ROS) and lipid oxygen species (LOS) are produced. • At low dose always ROS are prominent, at high dose LOS increases, independent of previous skin treatment as well as used wavelength. The topical photodynamic therapy (PDT) is mainly used in the treatment of dermato-oncological diseases. The distribution and functionality of the photosensitizer Tetrahydroporphyrin-Tetratosylat (THPTS) was investigated using microscopic and spectroscopic methods after topical application to excised porcine skin followed by irradiation. The distribution of THPTS was determined by two-photon tomography combined with fluorescence lifetime imaging (TPT/FLIM) and confocal Raman microspectroscopy (CRM). The radicals were quantified and characterized by electron paramagnetic resonance (EPR) spectroscopy. Results show a penetration depth of THPTS into the skin down to around 12 ± 5 µm. A penetration of THPTS through the stratum corneum was not clearly observable after 1 h penetration time, but cannot be excluded. The irradiation within the phototherapeutic window (spectral range of visible and near infrared light in the range ≈ 650–850 nm) is needed to activate THPTS. An incubation time of 10 min showed the highest radical production. A longer incubation time affected the functionality of THPTS, whereby significant less radicals were detectable. During PDT mainly reactive oxygen species (ROS) and lipid oxygen species (LOS) are produced. Overall, the irradiation dose per se influences the radical types formed in skin. While ROS are always prominent at low doses, LOS increase at high doses, independent of previous skin treatment and the irradiation wavelength used. [ABSTRACT FROM AUTHOR]

Background: Central serous chorioretinopathy (CSC) is characterized by an accumulation of subretinal fluid (SRF) in the macula. It is usually treated by laser photocoagulation or photodynamic therapy (PDT) with consisting of different doses and power. This study aimed to compare the efficacy of half-dose PDT and one-third-dose PDT in chronic or recurrent CSC.Methods: A retrospective review of patients with chronic or recurrent CSC who were treated with either a half-dose or one-third-dose PDT, and had follow up 12 months afterwards. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and resolution of subretinal fluid (SRF) at baseline as well as 1, 3, 6 and 12 months post-PDT were assessed.Results: Forty-six eyes and 20 eyes received half-dose and one-third-dose PDT, respectively. The study showed efficacy of the one-third-dose PDT compared with half-dose PDT in BCVA improvement (0.10±0.04 logMAR for one-third-dose versus 0.17±0.04, for half-dose, P=0.148) and CRT improvement (125.6±24.6 μm for one-third-dose versus 139.1±16.54, for half-dose, P=0.933) at 12 months. The SRF recurrence rate was significantly higher in the one-third-dose PDT group compared with the half-dose PDT group (40.0% versus 15.2%, P=0.027) at 12-months.Conclusion: At 12 months, the one-third-dose PDT was effective in terms of BCVA and CRT improvement, when compared with half-dose PDT. However, this study showed that one-third-dose PDT had a higher recurrence rate of SRF. [ABSTRACT FROM AUTHOR]

The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm−2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors. [Display omitted] • Two biotin-conjugated Ru(II) complexes with AIE characteristics were synthesized. • Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. • Ru2 had potent targeting abilities for A549 cells and mitochondria. • Ru2 could enhance photodynamic therapy by disrupting cellular redox balance. • Ru2 could suppress tumor growth in A549 xenograft-bearing mice under 460 nm light. [ABSTRACT FROM AUTHOR]

Since tyrosine kinase inhibitor (TKI) could reverse ABCG2-mediated drug-resistance, novel chlorin e 6 -based conjugates of Dasatinib and Imatinib as photosensitizer (PS) were designed and synthesized. The results demonstrated that conjugate 10b showed strongest phototoxicity against HepG2 and B16-F10 cells, which was more phototoxic than chlorin e 6 and Talaporfin. It could reduce efflux of intracellular PS by inhibiting ABCG2 in HepG2 cells, and localize in mitochondria, lysosomes, golgi and ER, resulting in higher cell apoptosis rate and ROS production than Talaporfin. Moreover, it could induce cell autophagy and block cell cycle in S phase, and significantly inhibit tumor growth and prolong survival time on BALB/c nude mice bearing HepG2 xenograft tumor to a greater extent than chlorin e 6. Consequently, compound 10b could be applied as a promising candidate PS due to its good water-solubility and stability, low drug-resistance, high quantum yield of 1O 2 and excellent antitumor efficacy in vitro and in vivo. [Display omitted] • The conjugates of chlorin e 6 with Dasatinib or Imatinib were synthesized. • In vitro PDT antitumor activities of all target compounds were investigated. • In vivo antitumor potency and mechanism of preferred compound 10b were evaluated. • In vitro PDT antitumor efficacy of 10b was better than chlorin e 6 and talaporfin. • In vivo PDT antitumor efficacy of 10b was superior to chlorin e 6. [ABSTRACT FROM AUTHOR]

[Display omitted] Innovative anticancer therapies based on the activation of the immune system offer promise in the battle against cancers resistant to traditional treatments. Examples of such therapeutic approaches include, along with various types of immunotherapies, photodynamic therapy (PDT). PDT is a photochemistry-based strategy that results not only from its direct effects on cancer cells but also from disruption of tumor vasculature and activation of the host immune system. However, to achieve therapeutic success manifested in the eradication of the primary tumor and distant metastases, it is necessary to design suitable photosensitizers (PSs) with the desired optical and photophysical properties to enable efficient generation of ROS under tumor microenvironmental (TME) conditions, especially hypoxia. Thus, in this review particular attention is paid to the photochemical properties of PSs, notably the sufficiently long-lived triplet states and mechanisms of energy/electron transfer reactions. Photogenerated ROS initiate inflammatory reaction, expression of heat-shock proteins, infiltration of immune cells and long-term immune memory. These unique features of PDT give new possibilities to combine PDT with agents stimulating immune response as well as with immunotherapy, especially based on PD-1/PD-L1 blockade. Most of the systems explored in this aspect so far are either derivatives of naturally occurring metal complexes (Heme , Chlorophyll a, and Bacteiochorophyll a - inspired PSs), synthetic (metallo)porphyrins, and (metallo)phthalocyanines or hybrid materials containing metal nanoparticles. This work also summarizes recent reports on the synthesis of antibody-PS conjugates with desired spectroscopic and photochemical properties along with enhanced selectivity and biological activity. Finally, the most notable drawbacks of PDT are presented, and a scenario is outlined for the development of PDT alone, and combined with immunotherapy to overcome these challenges in the future. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can't be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a method of the treatment of localized cancers, based on a photochemical reaction between a light-activated molecule or photosensitizer (PS), light, and molecular oxygen. Correct choice of PS is of fundamental importance for PDT efficacy. Despite numerous studies in this field, most known PS have some drawbacks, e.g. lack of specificity and aggregation in aqueous media. Consequently, the search for an ideal PS is essential for further development of PDT. Here we review classification and analyse main features of different generations of PS and describe the mechanisms of their action. Various methods of targeted delivery of PS to tumor cells are discussed. The advantages of PS nanoparticles with the effect of aggregation-induced emission (AIE) over the classic photosensitizers are presented. A possibility of practical application of such light-emitting structures in cancer phototherapy is shown. Photodynamic therapy (PDT) is a method of the treatment of localized cancers, based on a photochemical reaction between a light-activated molecule or photosensitizer (PS), light, and molecular oxygen. Correct choice of PS is of fundamental importance for PDT efficacy. Despite numerous studies in this field, most known PS have some drawbacks, e.g. lack of specificity and aggregation in aqueous media. Consequently, the search for an ideal PS is essential for further development of PDT. Here we review classification and analyse main features of different generations of PS and describe the mechanisms of their action. Various methods of targeted delivery of PS to tumor cells are discussed. The advantages of PS nanoparticles with the effect of aggregation-induced emission (AIE) over the classic photosensitizers are presented. A possibility of practical application of such light-emitting structures in cancer phototherapy is shown. [ABSTRACT FROM AUTHOR]

Abstract Photodynamic therapy (PDT) is reported to be a promising technique to eradicate various cancers. As most of the photosensitizers (PSs) are hydrophobic in nature, thus, the effective delivery of PSs at the targeted site is the main hurdle associated with PDT. Zinc phthalocyanine and Zinc naphthalocyanine are reported as good PSs, however, highly hydrophobic characteristics restrict their use for clinical applications. To circumvent this limitation here we developed the advanced polymer-based nano-delivery system having polyethylene glycol (PEG) coated polymeric core with ~90% PS encapsulation. The PEG coating was responsible for the stabilization of probe in the physiological environment and storage conditions. The developed theranostic probes showed efficient in vitro fluorescence and singlet oxygen quantum yields upon irradiation with 620–750 nm (30 mW/cm2) light. The clathrin-mediated endocytosis (CME) based mechanism of cellular internalization was evaluated. The fluorescence of treated MCF-7 cells showed the ability of the probes as imaging agents. Moreover, up to 65% cell inhibition showed their cytotoxic efficiency. Further, comparatively higher tumor-accumulation of PSs without significant hepato/nephro-toxicity shown in vivo experimentation using breast tumor-bearing female Sprague Dawley (SD) rats suggested the featured passive targeting ability of preparations and clinically safe to be used. The study explored the exceptional delivery system for hydrophobic PSs with commendable theranostic applications. Graphical Abstract Unlabelled Image Highlights • The advanced delivery system for highly hydrophobic photosensitizers have been developed in a simple one step method. • The probes were physiologically stable, having good fluorescence and adequate singlet oxygen quantum yields. • These probes have good pharmacokinetics, passive targeting ability and negligible hepato/nephro-toxicity. • The probes have shown commendable theranostic property through fluorescence imaging and photodynamic therapy. [ABSTRACT FROM AUTHOR]

Abstract Herein, we report the synthesis and spectroscopic characterization of novel Near Infra-Red (NIR) pentamethine cyanine dyes, as potential photosensitizers for Photodynamic Therapy (PDT) characterized by a strong absorption in the tissue transparency window (600–800 nm). The heteroaromatic benzoindolenine ring of various symmetrical cyanine dyes has been differently functionalized and quaternarized as a result of a structure-activity study and to determine the substituent effect on the cellular uptake, ROS production and photodynamic activity. These probes present low cytotoxicity in dark, but promote phototoxic effect, upon irradiation, in human fibrosarcoma cell line (HT-1080) with interesting and unexpected structure to property activity. Highlights • A new series of symmetrical penthametine cyanine dyes have been synthesized. • The dyes have been proposed as photosensitizers (PSs) for Photodynamic Therapy (PDT). • The PSs show strong absorption in the tissue transparency window (600–800 nm). • The PSs have low cytotoxicity in dark, but promote phototoxic effect, upon irradiation, in human fibrosarcoma cell line. [ABSTRACT FROM AUTHOR]

Abstract Zn-based phthalocyanine acts as drug or photosensitizer in photodynamic therapy (PDT) for the treatment of cancer cells. The activated zinc octacarboxyphthalocyanine (ZnPcOC) reacts with oxygen, to generate reactive oxygen species for the damage of melanoma cancer cells, Me45. This in vitro study aimed at investigating the cytotoxic effects of different concentrations of ZnPcOC activated with a diode laser (λ = 685 nm) on Me45, and normal human fibroblast cells, NHDF. To perform this study 104 cells/ml were seeded in 96-well plates and allowed to attach overnight, after which cells were treated with different concentrations of ZnPcOC (10, 20 and 30 μM). After 4 h, cells were irradiated with a constant light dose of 2.5; 4.5 and 7.5 J/cm2. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT viability assay. Data indicated that high concentrations of ZnPcOC (30 μM) in its inactive state are not cytotoxic to the melanoma cancer cells and normal fibroblasts. Moreover, the results showed that photoactivated ZnPcOC (30 μM) was able to reduce the cell viability of melanoma and fibroblast to about 50%, respectively. At this photosensitizing concentration the efficacy the treatment light dose of 2.5; 4.5 and 7.5 J/cm2 was evaluated against Me45 cells. ZnPcOC at a concentration of 30 μM activated with a light dose of 2.5; 4.5 and 7.5 J/cm2 was the most efficient for the killing of melanoma cancer cells. Melanoma cancer cells after PDT with a photosensitizing concentration of 30 μM ZnPcOC and a treatment light dose of 2.5; 4.5 and 7.5 J/cm2 showed certain pro-apoptotic characteristics, such as direct inducer (early apoptosis) and long-term inducer, also (late apoptosis). This concludes that low concentrations of ZnPcOC, activated with the appropriate light dose, can be used to induce cell death in melanoma cells via ROS-induces apoptosis pathway, what was confirmed with cytometric ROS measurements. Our in vitro study showed that ZnPcOC mediated photodynamic therapy is an effective treatment option for melanoma Me45 cancer cells. 30 μM of ZnPcOC with the treatment light dose of 2.5 J/cm2 from a LED diode laser source, with a wavelength of 685 nm, was adequate to destroy melanoma cancer cells via ROS-induced apoptosis pathway, with low killing effects on healthy NHDF normal fibroblasts. Highlights • ZnPcOC is a good photosensitizer tested in PDT therapy against Me45 cancer cells. • A pro-apoptotic activity is observed as early apoptosis after exposition, followed by 4 h of preincubation with ZnPcOC. • ZnPcOC complex is stable in DMSO upon light (λ = 685 nm) irradiation. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been used clinically for treating various diseases including malignant tumors. The main advantages of PDT over traditional cancer treatments are attributed to the localized effects of the photochemical reactions by selective illumination, which then generate reactive oxygen species and singlet oxygen molecules that lead to cell death. To date, over- or under-treatment still remains one of the major challenges in PDT due to the lack of robust real-time dose monitoring techniques. Time-resolved fluorescence (TRF) provides fluorescence lifetime profiles of the targeted fluorophores. It has been demonstrated that TRF offers supplementary information in drug-molecular interactions and cell responses compared to steady-state intensity acquisition. Moreover, fluorescence lifetime itself is independent of the light path; thus it overcomes the artifacts given by diffused light propagation and detection geometries. TRF in PDT is an emerging approach, and relevant studies to date are scattered. Therefore, this review mainly focuses on summarizing up-to-date TRF studies in PDT, and the effects of PDT dosimetric factors on the measured TRF parameters. From there, potential gaps for clinical translation are also discussed.

Photobiomodulation (PBM) and photodynamic therapy (PDT) share similar mechanisms but have opposite aims. Increased levels of reactive oxygen species (ROS) in the target tissue in response to light combined photosensitizer (PS) application may lead to cell proliferation or oxidative damage depending on the ROS amount. The purpose of the present study is to investigate the effect of indocyanine green (ICG)-mediated PBM on osteoblast cells by measuring cell viability, proliferation, alkaline phosphatase (ALP) activity, mineralization, and gene expressions of three phenotypic osteoblast markers. A diode laser irradiating at 809 nm (10 W output power, 50 mW/cm2 power density) was used at 0.5, 1, and 2 J/cm2 energy densities (10, 20, and 40 s respectively) was applied following ICG incubation. No inhibitory effect was observed in cell viability and proliferation according to the (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Alamar Blue assays. ICG-mediated PBM did not alter cell viability but increased ALP activity and enhanced mineralization of existing osteoblasts. These results were also confirmed by real-time polymerase chain reaction (RT-PCR) analysis of osteoblastic markers. PS can be combined to PBM not only to damage the malignant cells as aimed in PDT studies, but also to promote cellular activity. The findings of this in vitro study may contribute to in vivo studies and ICG-mediated PBM can have promising outcomes in bone healing and regeneration therapies in future. [ABSTRACT FROM AUTHOR]

The development of multifunctional carriers incorporating genetic and photodynamic therapy (PDT) for synergistic antitumor treatment has attracted intensive interests very recently. However, most of the currently reported systems employ passive gene release strategies depending on tumor microenvironment, which are negatively affected by the heterogeneity of cancer cells, thus resulting in limited controllability in therapeutic progress. Herein, a novel photo-responsive hollow silica nanoparticle (HNP)-based gene and photosensitizer (PS) co-delivery nanovehicle is designed for dual-wavelength light-triggered synergistic gene and PDT therapy. The resultant HNP conjugated with PDMAEMA polycation through a 405-nm light-cleavable Cou-linker, namely, HNP-Cou-PD, exhibits excellent gene condensation capacity, good biocompatibility, outstanding PS loading ability, and light-triggered gene release properties. HNP-Cou-PD with Chlorin e6 (Ce6) loaded inside the silica cavity and a plasmid encoding caspase-8 gene (CSP8) attached to the PDMAEMA outside layer (Ce6-HNP-Cou-PD/CSP8) has been proven to possess better antitumor effects under the irradiation of pre-405-nm and post-670-nm light both in vitro and in vivo because of the light-triggered intracellular gene release and reactive oxygen species (ROS) generation. Therefore, HNP-Cou-PD designed as a gene and PS co-delivery carrier might have promising applications in the future to precisely treat various types of cancers. Statement of Significance Multifunctional carriers incorporating genetic and photodynamic therapy (PDT) have drawn intense attention very recently, ascribing to their enhanced anticancer effects. However, in the present gene and PDT synergistic system, gene release strategies passively relying on tumor microenvironment often result in no or poor controllability compared with PDT (a spatial and temporal therapeutic modal), which may hinder their synergistic efficacy, especially in an on-demand manner. To resolve this problem, we designed a hollow silica nanoparticle-based dual-wavelength light-responsive gene and photosensitizer (PS) co-delivery platform to achieve photo-triggered gene and PDT synergistic therapy. We believe that our work may have extensive application prospects in precise treatment of various cancers and be of interest to the readership. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is among the most promising therapeutic options that have appeared in oncology within the last 30 years, taking into account the complex interaction between light, photosensitizer, molecular oxygen and intracellular structures. The use of various photosensitizing drugs and various light sources contributes to the complexity of PDT studies. Some distinguished examples with clinical dermatologic applications are shown in this paper. [ABSTRACT FROM AUTHOR]

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by low energy directed light. In this way, it is possible to achieve the destruction of the tumor tissue by safeguarding the surrounding healthy structures. Our study describes the clinical uses and efficacy of photodynamic therapy in ocular oncology. [ABSTRACT FROM AUTHOR]

In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced. [ABSTRACT FROM AUTHOR]

Background: To evaluate the macular sensitivity changes after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR).Methods: Eighteen patients (26 eyes) with chronic CSCR were recruited in the same hospital between April 2011 and December 2012. All patients were treated with one session of half-dose PDT after complete ophthalmic examination. Macular sensitivity examination was performed at baseline and 1, 3 and 6 months post-treatment. Mean sensitivity (MS) of the central 10 degrees (10°) and 4 degrees (4°), mean deviation (MD) and pattern standard deviation (PSD) on automated static perimetry (Humphrey Field Analyzer II-750) were used for analysis.Results: There was significant improvement of the 10°MS from baseline (29.76 ± 1.51 dB) to 1 month (31.74 ± 1.56 dB), 3 months (31.51 ± 1.38 dB) and 6 months (31.19 ± 1.61 dB) after treatment (P < 0.001). The 4°MS was also significantly improved with half-dose PDT from baseline (28.96 ± 1.78 dB) to 1 month (32.41 ± 1.66 dB), 3 months (32.46 ± 1.50 dB) and 6 months (31.90 ± 1.84 dB) post-treatment (P < 0.001). MD was improved from baseline (-3.39 ± 0.89 dB) to 1 month (-1.96 ± 0.29 dB), 3 months (-1.94 ± 0.29 dB) and 6 months (-2.45 ± 0.13) post-treatment (P = 0.004). PSD also improved from 1.97 ± 0.24 dB at baseline to 1.47 ± 0.27 dB, 1.34 ± 0.24 dB, and 1.53 ± 0.24 dB (P = 0.001) at 1, 3 and 6 months after treatment, respectively.Conclusion: Macular sensitivity in CSCR can be improved by half-dose PDT, along with improvement of visual acuity and retinal thickness. The treatment outcome at 1 month may be a predictor of the final treatment response. [ABSTRACT FROM AUTHOR]

Two novel silicon(IV) phthalocyanines bearing 1,3-bis[3(dimethylamino)phenoxy]propan-2-ol or 1,3-bis[3(diethylamino)phenoxy]propan-2-ol groups at their axial positions were synthesized. These phthalocyanines were converted into their water soluble derivatives by the quaternization reaction with methyl iodide. The quaternized phthalocyanines show excellent solubility aqueous solutions without any aggregation which makes them potential photosensitizers for use in photodynamic therapy (PDT). For this reason, the photophysical and photochemical properties such as fluorescence quantum yields, lifetimes, singlet oxygen generation and photodegradation of both non-ionic ( 3 and 5) and quaternized cationic silicon(IV) phthalocyanines were investigated. Furthermore, the cytotoxicity of PDT was determined by colorimetric proliferation assay against to hepatocellular carcinoma (HuH-7) cancer cells. In this study, the cells were incubated with a novel water soluble silicon(IV) phthalocyanine derivatives and thereafter the cells were illuminated using broad-band incoherent light source. Graphical abstract: [ABSTRACT FROM AUTHOR]

Objective: Photodynamic therapy (PDT) is an alternative treatment for cancer, which involves the administration of a photosensitizing agent that is activated by light at a specific wavelength. This illumination causes after a sequence of photoreactions, the production of reactive oxygen species responsible for the death of the tumor cells but also the degradation of the photosensitizing agent, which then loose the fluorescence properties. The phenomenon is commonly known as the photobleaching process and can be considered as a therapy efficiency indicator. Methods: This paper presents the design and validation of a real-time controller able to track a preset photobleaching trajectory by modulating the light impulses width during the treatment sessions. Results: This innovative solution was validated by in vivo experiments that have shown a significantly improvement of reproducibility of the interindividual photobleaching kinetic. Conclusion: We believe that this approach could lead to personalized PDT modalities. Significance: This work may open new perspectives in the control and optimization of photodynamic treatments. [ABSTRACT FROM PUBLISHER]

Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Hypericin is an endoplasmic reticulum (ER)-located photosensitizer, which causes oxidative damage to ER during photodynamic therapy (PDT). Hypericin-mediated PDT (HY-PDT) has been confirmed to enhance chemo-sensitivity of oxaliplatin (L-OHP) in colon cancer cells. The present study reveals that autophagy plays a key role in chemosensitization during HY-PDT. We proved pro-death autophagy was required for sensitization and HY-PDT/L-OHP antitumor synergism. High dosage of HY-PDT induced autophagic cell death; while low dose of HY-PDT predominantly triggered protective autophagy and promoted cell proliferation. Low dose of HY-PDT reduced the cytotoxicity of L-OHP in oxaliplatin-resistant colon cancer cells. Different level of autophagy therefore contributed to the opposite effect of HY-PDT on cell fate and chemo-sensitivity. Furthermore, we revealed the role of CHOP as a regulator connecting pro-survival and pro-death autophagy under ER damage. High dose of HY-PDT induced massive ROS generation and severe ER stress, which then led to induction of CHOP. CHOP thereby activated CHOP/TRIB3/Akt/mTOR cascade and triggered autophagic cell death. Additionally, when apoptotic pathway was blocked, cells treated with high dose of HY-PDT preferentially underwent death through autophagic pathway. On the other hand, suppression of autophagy made cells more vulnerable to apoptosis under low dose of HY-PDT. These results provided new evidences for the clinical application of ER-targeting PDT in modifying chemosensitivity of colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

To develop a water-soluble and tumor-targeted photosensitizer for photodynamic therapy (PDT), a porphyrin framework containing the metal ion gallium(III) was combined with platinum(II)-based groups to produce two new pentacationic metalloporphyrinates, Ga-4cisPtTPyP (5,10,15,20-tetrakis{ cis -diammine-chloro-platinum(II)}(4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate) and Ga-4transPtTPyP (5,10,15,20-tetrakis{trans-diammine-chloro-platinum(II)} (4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate). Both complexes exhibited high singlet oxygen quantum yields (Φ ∆ ) and remarkable photocytotoxicity with appreciable phototoxic indexes (PIs). In particular, Ga-4cisPtTPyP showed a low IC 50 value (Colon 26: 0.12 μM; Sarcoma 180: 0.08 μM) under illumination and its PI up to 1000. With outstanding tumor accumulation (tumor/muscle ratio > 9), Ga-4cisPtTPyP almost completely inhibited tumor growth over two weeks in an in vivo PDT assay. These results imply that Ga-4cisPtTPyP could be a promising anticancer agent for use in PDT. [ABSTRACT FROM AUTHOR]

This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2a and TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS2a and TPCS2a were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate reactive oxygen species to induce cell death in tumors. Photosensitizers have been progressively developed, from first to third generation, with improvements in cell specificity, reduced side effects and toxicity, increased sensitivity for irradiation and reduced persistence of photosensitizer in healthy cells. These improvements have been achieved by basic comparative experiments between current and novel photosensitizers using cell lines; however, photosensitizers should be carefully evaluated because they may have cell type specificity. In the present study, we compared a third-generation photosensitizer, ß-mannose-conjugated chlorin (ß-Mchlorin), with the second generation, talaporfin sodium (NPe6), using seven different rat and human cell lines and a neuronal/glial primary culture prepared from rat embryos. NPe6 was more effective than ß-Mchlorin in human-derived cell lines, and ß-M-chlorin was more effective than NPe6 in rat primary cultures and rat-derived cell lines, except for the rat pheochromocytoma cell line, PC12. These differences of phototoxicity in different cell types are not because of differences in photosensitivity between the photosensitizers, but rather are associated with different distribution and accumulation rates in the different cell types. These data suggest that evaluation of photosensitizers for PDT should be carried out using as large a variety of cell types as possible because each photosensitizer may have cell type specificity [ABSTRACT FROM AUTHOR]

Gold nanostructures of two different shapes (spheres and rods) were synthesized to form a colloidal hybrid system with 5,10,15,20-tetrakis( N -methylpyridinium-4-yl)porphyrin tosylate salt (H 2 TM4PyP(OTs) 4 ) (POR) for applications in photodynamic therapy (PDT) using light in the visible spectral range. Electron paramagnetic resonance (EPR) experiments in combination with spin trapping were used for the detection of reactive oxygen species (ROS) and evaluation of the efficiency of these novel hybrid systems as photosensitizers. It is shown that the hybrid system consisting of gold nanorods (AuNR) and porphyrin (POR) is by far more efficient than its isolated components. This enhanced efficiency is explained by a synergetic effect between the AuNR and the porphyrin, wherein a rapid energy transfer from the former to the latter produces a large amount of singlet oxygen followed by its conversion into hydroxyl radicals. The mechanism was investigated using different spin traps and different ROS inhibitors. On the other hand, spherical gold nanoparticles (AuNP) do not show this synergetic effect. The synergetic effect for gold nanorods/POR hybrid is attributed to a larger field enhancement close to the gold nanorod surface in addition to the electrostatic attraction between the components of the hybrid system. [ABSTRACT FROM AUTHOR]

Sixteen porphyrins, including neutral, anionic and cationic meso -(aryl)porphyrins and meso -(1-methyl-4-pyridinium)porphyrins were herein evaluated in terms of their photosensitizing properties against HaCaT keratinocytes. After an initial screening, the cationic porphyrins were studied in more details, by both determining their log P OW and performing PDT assays in lower porphyrin concentrations. Porphyrins presenting two or more adjacent positively charged groups, directly linked to the macrocycle meso positions, appeared to be the most effective photosensitizers. The present study also included the dicationic 5,10-diphenyl-15,20-di(1-methylpyridinium-4-yl)porphyrin ( 14b ), which has previously shown promising results on a psoriasis-like in vivo model. Overall results indicated that the beneficial effect related to porphyrins on psoriasis can be related to the decreasing of keratinocyte viability. Furthermore, some of the cationic porphyrins studied appeared as candidates to be utilized as photosensitizers for psoriasis treatment. [ABSTRACT FROM AUTHOR]

Objective and background: The aim of this in vitro study was to compare the efficiency of a photodynamic therapy (PDT) technique employing rose bengal (RB) and methylene blue (MB) as photosensitizers (PSs) to reduce the viability of Enterococcus faecalis, a well-known pathogen found in root canal systems. Currently, in several clinical applications, including in the field of endodontics, MB is employed in association with a red laser source for the photoinactivation of pathogenic bacteria. Methods: In this study, MB was used at 0.01% (31.2 mol/L) in association with a red (660 nm) laser as the excitation source in the MB group (MBG). Alternatively, the same test was performed with RB (25 mol/L) that was associated with a green (532 nm) light laser source in the RB group (RBG). A saline solution (0.9%) was used in the control group. The colony-forming units per milliliter (CFU/mL) were calculated after 24 h of incubation at 37°C, and the statistical analysis was performed using ANOVA. Results: The results showed a significant reduction in the CFU/mL in the RBG group (0.12 × 108) compared with the control (2.82 × 108) and MBG groups (2.66 × 108). For the concentration and laser intensity employed in the experiments, the MBG group repeatedly showed no significant reduction in bacterial counts compared with the control. Therefore, the best result regarding the reduction of E. faecalis viable cells was obtained with RB as the PS. Conclusions: PDT may be improved if RB is used in association with a green light laser source for the inactivation of E. faecalis. [ABSTRACT FROM AUTHOR]

• A novel aza-BODIPY with phthalonitrile substituents was synthesized. • Spectrophysical and spectrochemical properties were investigated. • Singlet oxygen quantum yield and fluorescence quantum yield were quantified. • Photodynamic efficiency as a photosensitizer for PDT was investigated. • The cytotoxicity towards breast cancer cell line, MCF-7 cells, was investigated. In photodynamic therapy (PDT), reactive oxygen species (ROS) are generated through dynamic interactions between light of a specific wavelength, a photosensitizer (PS) and molecular oxygen. Nowadays, there has been an increment in the number of studies evaluating the possible utilization of BF 2 chelated tetraarylazadipyrromethanes (aza-BODIPYs) as photosensitizers in PDT. In this study, a novel aza-BODIPY with phthalonitrile substituents was synthesized by the esterification reaction of a phthalonitrile derivative namely, 4-((3,4-dicyanophenyl)sulphanyl)benzoic acid with an aza-BODIPY bearing hydroxy groups on the para positions of distal phenyl groups. Aza-BODIPY compound bearing phthalonitrile substituents was characterized by using UV–Vis, fluorescence, 1H-NMR and mass spectroscopy techniques. Photophysical and photochemical properties including fluorescence quantum yield and singlet oxygen yield were determined. In order to explore its photodynamic efficacy, it was tested on a breast cancer cell line (MCF-7 cells) and on a normal healthy cell line (L929 cells) through dark and light cytotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel DTE-based photoswitchable AIE photosensitizer has been developed. • It showed excellent AIE properties and photochromism in different solvents. • Excellent photoswitching behavior was observed in the water-soluble nanosystem. • Reversible control of 1O 2 generation was achieved under 420 nm light irradiation. • It was successfully applied in imaging-guided photocontrolled antimicrobial PDT. The photosensitizer system that allows for reversible noninvasive control over singlet oxygen generation (1O 2) is in great demand for precise photodynamic therapy (PDT) aimed at reducing non-specific damage to the normal cells or tissues. However, they often suffer from fluorescence quenching and insufficient 1O 2 generation due to aggregation-caused quenching (ACQ) phenomenon in a hydrophilic and physiological environment, severely limiting their applications in both imaging and PDT therapy. Herein, a novel positively charged photoswitchable photosensitizer with aggregation-induced emission (AIE) has been rationally designed and successfully developed, in which pyridinium-tetraphenylethylene (Py-TPE) photosensitizing fragment and dithienylethene (DTE) switch unit were covalently linked through a flexible C4 chain enabling efficient intramolecular energy transfer between both functional entities, thus allowing for reversible control of 1O 2 generation. Preliminary evaluation of the photophysical properties revealed excellent AIE properties and photoswitching behavior in various solvents. Furthermore, the nanoparticles (NPs) fabricated by the amphiphilic Pluronic F127 exhibited excellent photochromic performance in the aqueous medium. Significantly, 1O 2 generation in the closed NPs was suppressed by the competitive energy transfer, while the generation of 1O 2 in the open NPs was activated upon light irradiation, demonstrating its reversible control over 1O 2 generation under irradiation with 420 nm light. As expected, it has been proved to perform well in specific bacterial discrimination and photocontrolled antimicrobial PDT against Staphylococcus aureus (S. aureus) in vitro. [ABSTRACT FROM AUTHOR]

• Novel pyropheophorbide a -based dimers linked via 31-ether linkage were synthesized. • In vitro photocytotoxicity and mechanism of dimers 5a and 5b were investigated. • In vivo PDT antitumor potency of dimers 5a and 5b had been evaluated. • Dimers 5a and 5b could enhance intracellular ROS to a greater extent than Talaporfin. • Dimers 5a and 5b had stronger in vitro and in vivo PDT antitumor efficacy than Talaporfin. In this paper, the dimer of pyropheophorbide a via 31-ether bond linkage as novel chlorin photosensitizers (PSs) for tumor photodynamic therapy (PDT) was designed and synthesized. We have separated it into two stereoisomers 5a (less polar) and 5b (more polar) by flash column chromatography and investigated their photophysical properties, PDT antitumor efficacy and mechanism. The results demonstrated that they should be a pair of epimers. Both dimers 5a and 5b showed stronger phototoxicity and higher dark-toxicity / phototoxicity ratio (> 350) against A549, HeLa and B16-F10 cells than their precursor 1 and Talaporfin. Moreover, photocytotoxicity and dark-cytotoxicity of 5b were both significantly higher than those of 5a , which seemed to be the first report that a couple of chlorin-based dimers stereoisomers via 31-ether linkage exhibited significant differences in vitro PDT antitumor efficacy. They could enhance intracellular ROS production to a greater extent than Talaporfin under light irradiation and also should have better in vivo PDT antitumor efficacy on C57BL/6 mice bearing B16−F10 tumor than Talaporfin at the same dosage. As a result, dimers 5a and 5b are promising photosensitizer for PDT applications because of its strong absorption in the phototherapeutic window (λ max = 666 nm), relatively high ROS yield and dark toxicity/phototoxicity ratio, and excellent PDT antitumor efficacy. We describe the synthesis and biological properties of two novel chlorin-based dimer stereoisomers (5a and 5b) of pyropheophorbide a via its 31-ether linkage as potent photosensitizer, which are promising antitumor candidates for PDT applications due to their strong absorption at long wavelength (λ max = 666 nm), high dark toxicity/phototoxicity ratio, excellent in vitro and in vivo PDT antitumor efficacy. [Display omitted] [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) relies on the generation of cytotoxic singlet oxygen (1O 2) from an otherwise nontoxic photosensitizer accumulated in tumor tissue to treat cancer. However, PDT of uveal melanoma, the most common adult intraocular cancer, using potent porphyrin derivatives as photosensitizers has shown limited therapeutic efficacy due to low bioavailability and 1O 2 yield. Here, considering the uveal melanoma microenvironment of endogenous melanin, which has a high absorption between 300 nm and 500 nm, we design a carbon dot-based photosensitizer that uses multiple different pathways to generate 1O 2. We conjugated gadolinium (Gd)-doped carbon dots (Gd@Cdots) with the porphyrin-derivatives chlorin e6 (Ce6) and verteporfin (Ver). The resulting nanoparticle (Gd@Cdots/Ce6/Ver) generates 1O 2 under UV irradiation mainly in cascade FRET from Gd@Cdots to Ce6 and then to Ver; the photoactivated Ver, in turn, transfers its energy to 3O 2 to generate 1O 2. In human uveal melanoma MUM-2B cells in vitro, Gd@Cdots/Ce6/Ver generated 7.1- and 2.4-fold higher production of hydroxyl radical (·OH) and superoxide anions (O 2 -·) following UV irradiation than Gd@Cdots, indicating greater induction of tumor cell apoptosis. In an orthotopic mouse model of uveal melanoma, PDT with Gd@Cdots/Ce6/Ver showed the same trend of superior potency in tumor growth inhibition. This photosensitizer design improves the PDT efficacy of uveal melanoma by enhancing the production of 1O 2 and should be of broad utility to other PDT. [Display omitted] • A cascade FRET photosensitizer for photodynamic therapy of ocular melanoma is developed. • The cascaded photosensitizer has highly coincident absorption light range with melanin which is highly expressed in ocular melanoma. • The cascaded FRET photosensitizer yield 1O 2 and ROS via multiple photoactivation pathways. • The cascaded photosensitizer shows superior potency in tumor growth inhibition and little side effect on normal tissues. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM) was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa), and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT) against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT) assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm²). Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role. [ABSTRACT FROM AUTHOR]