Skin Phototoxicity Research Articles

Near-infrared light and redox dual-activatable nanosystems for synergistically cascaded cancer phototherapy with reduced skin photosensitization

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was “double-locked” by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the “double-key”, which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

Porous organic polymer overcomes the post-treatment phototoxicity of photodynamic agents and maintains their antitumor efficiency

Since 1995, photodynamic therapy (PDT) has been utilized as an effective method for cancer treatment. However, the residues of photosensitizers in the normal tissues after PDT can be activated by sunlight to cause severe skin phototoxicity, for which currently there are no clinical solutions. As a result, post-PDT patients need to remain out of sunlight for up to five weeks, which produces great living and mental burdens for patients. Herein, we report that a biocompatible porous organic polymer (POP) with average 3.1 nm porosity is able to suppress the skin phototoxicity of clinically used porphyrin-based photodynamic agents (PDAs), including Photofrin, Talaporfin and Hiporfin, through an adsorption-elimination mechanism. Fluorescence titration and dialysis experiments show that POP can adsorb and retain the PDAs at a micromolar concentration. In vivo experiments demonstrate that POP can significantly suppress the skin phototoxicity caused by all the three PDAs without reducing their PDT efficacy. Statement of significanceUp to now, no efficient clinical treatment for the inhibition of post-PDT phototoxicity of clinically used porphyrin-based PDAs is available. In the manuscript, a water-soluble cationic porous organic polymer has been revealed to include three clinically used PDAs. In vivo experiments show that this inclusion remarkably reduces the content of PDAs in mouse skins, leading to significant alleviation of their post-PDT phototoxicity without no negative effect on their PDT efficacy. Thus, this work provides a strategy for overcoming the drawback of clinically used photodynamic agents.

Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy

Despite that photodynamic therapy (PDT) has been applied for the treatment of cancer and skin diseases for more than two decades, all clinically used photodynamic agents (PDAs) suffer the drawback of skin phototoxicity of PDAs, which requires patients to avoid exposure to natural light for weeks after treatment, but has so far lacked effective suppression methods. Here, we report that three-dimensional diamondoid supramolecular organic frameworks (SOFs), that possess well-defined 2.1-nm porosity, can be used to suppress the skin phototoxicity of Photofrin, HiPorfin and Talaporfin, three porphyrin-based PDAs which clinically receive the most wide applications by injecting SOF after PDT, via an adsorption and retention mechanism. Fluorescence and dynamic light scattering experiments confirm that the SOFs have strong interaction with PDAs, and can adsorb PDAs at a micromolar concentration, whereas dialysis experiments support that the adsorption leads to an important retention effect. In vitro and in vivo experiments reveal that SOFs have high biocompatibility. Studies with healthy and tumor-bearing mouse models demonstrate that, when the PDAs are administrated at a dose comparable with the clinical one, SOF can remarkably suppress sunlight-induced skin phototoxicity, whereas the PDT efficacy of mice treated with SOF post-PDT is maintained. This work provides an efficient strategy for the improvement of the safety of clinically used PDAs.

Skin-safe nanophotosensitizers with highly-controlled synthesized polydopamine shell for synergetic chemo-photodynamic therapy

Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced •OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.

Tumor Microenvironment Activated Chemodynamic–Photodynamic Therapy by Multistage Self‐Assembly Engineered Protein Nanomedicine

AbstractWhile cytotoxic reactive oxygen species (ROS) play an important role in fighting cancer, developing an activable ROS‐generating system to achieve highly specific cancer therapy with minimum side effects to normal tissues remains challenging. This work reports the development of a tumor microenvironment‐activable ROS‐generating system via multistage self‐assembly engineered protein‐based nanomedicine containing cascade enzymes and photosensitizers. The multistage self‐assembly‐induced aggregation not only prevents the premature exposure of cascade enzymes to produce toxic by‐products in noncancerous sites, but also quenches the photosensitizers to diminish skin phototoxicity, contributing to effective self‐protection of normal tissues. Once triggered by the intratumoral reduction microenvironment, the aggregation effect is unlocked to expose cascade enzymes and recover the photosensitivity, which can decompose intratumor glucose for hydroxyl radical generation and respond to external laser irradiation for singlet oxygen production respectively, realizing tumor‐specific chemodynamic–photodynamic combinational therapy. This work demonstrates a protein‐based multistage self‐assembly approach for ROS‐mediated cancer‐specific therapy with effective self‐protection, offering a powerful strategy for nanomedicine design and more precise cancer therapy.

Tandem mass spectrometry of aqueous extract from Ficus dubia sap and its cell-based assessments for use as a skin antioxidant

Since 2006, Ficus dubia has been reported as a new Ficus species in Thailand. As per our recent report, the red-brown aqueous extract of F. dubia sap (FDS) has been determined to strongly exhibit in vitro anti-radicals. However, the phytochemicals in the FDS extract related to health-promoting antioxidation have not been explored. Thus, in this study, we aimed to investigate the chemical components of the F. dubia sap extract by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC–ESI–MS/QTOF-MS) and its potential use in cosmetics in terms of cellular antioxidation on keratinocytes (HaCaT), phototoxicity, and irritation on 3D skin cell models following standard tests suggested by the Organization for Economic Cooperation and Development (OECD). It was found that the sap extract was composed of quinic acid and caffeoyl derivatives (e.g., syringoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, and dimeric forms of caffeoylquinic acids). The extract has significantly exhibited antioxidant activity against H2O2-induced oxidative stress in HaCaT cells. The cellular antioxidative effect of the FDS extract was remarkably dependent on the presence of 3- and 4-O-caffeoylquinic acid in the extract. Furthermore, the FDS extract showed negative results on skin phototoxicity and irritation. Overall, the results reveal that the FDS extract could be developed as a new antioxidant candidate for a skin healthcare product.

Clinical Practice of Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer.

Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.

Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad‐spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty‐eight articles met inclusion criteria, describing photo‐sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo‐testing. Available data on incidence, severity and clinical relevance of tetracyclines‐related photo‐sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

Porfimer Sodium Versus PS785 for Photodynamic Therapy (PDT) of Lung Cancer Xenografts in Mice

BackgroundLung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration–approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice. MethodsHuman non–small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT. ResultsPorfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point. ConclusionsPS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.

Evaluation of the skin phototoxicity of systemically administered pharmaceuticals in Sprague-Dawley rats.

In vivo phototoxicity testing is important for predicting drug-induced phototoxicity in humans. Currently, there is no internationally validated in vivo test method for the photosafety evaluation of pharmaceuticals. In this study, we evaluated the phototoxicity of systemically administered drugs using SD rats. We first determined the appropriate ultraviolet A (UVA) dose using 8-methoxypsoralen, a well-known phototoxic drug. Compared to lower and higher UVA doses, we found that a UVA dose of 10J/cm2 allowed for the detection of phototoxic responses in both a dose- and time-dependent manner. We next performed a phototoxicity study using seven pharmaceutical drugs which included known phototoxic and non-phototoxic drugs using a UVA dose of 10J/cm2. In order to improve the accuracy of our assessment, we evaluated both gross skin findings as well as histopathological findings. Using gross skin findings alone resulted in an accuracy of 85.7% which could be increased to 100% accuracy when the gross skin findings were combined with histopathological findings. This study suggests that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of systemically administered drugs in SD rats. In conclusion, we found that for studying drug-induced phytotoxicity, a 10J/cm2 UVA dose serves as the optimal radiation dose, and that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of the drugs.

ALP-Activated Chemiluminescence PDT Nano-Platform for Liver Cancer-Specific Theranostics

Photodynamic therapy (PDT) is a promising therapeutic approach that has been extensively applied in curing cancers. However, the limited penetration depth of external light makes PDT only practical for some superficial tumor treatments. Moreover, an external light irradiation might cause damages to adjacent normal tissues. Additionally, the poor targeting ability of PDT can lead to side effects like skin phototoxicity. Therefore, a PDT strategy addressing these drawbacks is urgently exploited. Herein, we constructed a chemiluminescence theranostics platform named MSN@H6L@β-CD@AMPPD NPs for liver cancer-specific, in situ diagnosis and therapy without an external light source. Through the interaction of host-guest, 3-[(2-spiroadamatane)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane] dioxetane, a chemiluminescence substrate of the liver cancer biomarker alkaline phosphatase was integrated with β-cyclodextrin. Then, the β-cyclodextrin was covalently bound to the mesoporous silica loaded with (4-carboxyphenyl) porphyrin to finally obtain the MSN@H6L@β-CD@AMPPD NPs. These NPs can be specifically hydrolyzed by the liver cancer alkaline phosphatase and lead to the liver cancer-targeting chemiluminescence. Subsequently, (4-carboxyphenyl) porphyrin was excited by the chemiluminescence through chemiluminescence resonance energy transfer and created both near-infrared fluorescence and 1O2. This strategy greatly promotes the penetration depth and targeting ability of the PDT. In brief, the platform accomplishes a PDT nano-theranostics for liver cancer and provides a method for the imaging, diagnosis, and therapy of tumors in deep tissue.

Cutaneous phototoxic reaction to intravenous micafungin in the outpatient setting: A case report

• Micafungin can be used for the management of azole-resistant CMC in STAT1-GoF. • Micafungin was identified as the probable cause of a phototoxic skin reaction. • More research on phototoxicity of micafungin and its metabolites is required. • Clinicians should remain aware of the potential for phototoxic reactions. Signal Transducer and Activator of Transcription 1 (STAT1) Gain of Function (GoF) mutations can predispose to chronic mucocutaneous candidiasis (CMC). Long term therapy with oral azole antifungals can result in resistance and the need to treat with alternatives such as echinocandins. A pan-azole-resistant Candida albicans was isolated from a mouth swab from a 39-year-old woman with lifelong CMC. Her condition warranted systemic treatment and this was achieved through daily infusions of micafungin, which the patient self-administered at home within the OPAT (Outpatient Parenteral Antimicrobial Therapy) service. The patient experienced a good and rapid clinical response. On day 18 of treatment the patient developed an itchy rash and presented back to our hospital on day 22. A diagnosis of phototoxic skin reaction, secondary to micafungin, was established through clinical history, signs, and investigations. Micafungin was withdrawn and the phototoxic reaction resolved without further intervention. The patient was maintained on amphotericin oral lozenges. More research into the phototoxic potential of micafungin and its metabolites is needed but clinicians should remain aware of the potential of phototoxicity in individuals treated in outpatient and OPAT settings.

Evaluation of skin phototoxicity of transdermally administered pharmaceuticals in Sprague-Dawley rats

Some drugs cause phototoxicity in humans when exposed to light, thus there is a need for an in vivo phototoxicity test to evaluate them. However, an in vivo phototoxicity test method to evaluate this has not been established. This study aimed to establish an in vivo phototoxicity test method for transdermally administered drugs. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. We found that a UVA dose of 15 J/cm2 was dose and time dependent response compared to other UVA doses. We performed the Minimum Erythema Dose (MED) test because UVB can cause skin irritation by itself and selected 0.01 J/cm2 as an appropriate dose of UVB. Using the selected UVA and UVB doses, we performed a phototoxicity study of 6 pharmaceutical drugs, which included phototoxic and non-phototoxic drugs. As a result of the phototoxicity test, 100% accuracy was obtained when compared with previous studies. In addition, we performed histopathology to confirm the new findings. We found that histopathology can be used as an additional indicator of phototoxicity test for transdermally administered drugs.

Photodynamic therapy in the treatment of patients with vulvar premalignant diseases. First experience of its use in Ukraine

Objective of the study was to evaluate the tolerability and effectiveness of photodynamic therapy (PDT) in patients with vulvar premalignant diseases.Materials and methods. Study was performed in 10 patients on the basis of the National Cancer Institute of Ukraine (Kyiv). Age of patients ranged from 31 to 67 years old (mean age 53.3 ± 3.6 years old). Diagnosis was made on the basis of medical history, complaints and clinical examination of patients, vulvoscopy and results of morphological examination of pathologically altered vulvar tissues. A drug of the chlorine series “Photolon” (RUE “Belmedpreparaty”, Republic of Belarus) in doses from 1 to 2.5 mg/kg was used as a photosensitizer (FS). Photoirradiation of pathologically altered foci was performed 3–4 hours after the end of the FS infusion using a laser coagulator universal “Lika-surgeon” (“Photonics Plus”, Ukraine, λ = 660 nm) with a radiation power of 0.4 W in exposure doses of 100 up to 150 J/cm2. PDT tolerability was assessed basing on the frequency and severity of adverse reactions (CTCAE, version 3.0). PDT effectiveness was assessed basing on the presence/absence of complaints, data from visual observation of changes in the area of treated lesions and morphological examination data at 3 and 6 months after treatment (WHO criteria).Results. No serious adverse reactions associated with FS infusion and PDT session were observed: no allergic reactions (Quincke’s edema, urticaria, drop in blood pressure, bronchospasm), no symptoms of skin phototoxicity. There was remission of clinical symptoms (itch in the area of vulva) in the treated pathological centers and high frequency of clinical and morphological regressions in the control observation terms of patients.Conclusion. Obtained results indicate the relevance and prospects of further researches in the field of laser technology and PDT as options for organ-preserving treatment of vulvar premalignant diseases

Abstract A02: Photodynamic therapy in combination with immunotherapy enhances the long-term cure of bladder cancer in tumored mice

Abstract Introduction and Objectives: To investigate the utility of combination approach for treating bladder cancer, mice bearing UMUC3 (human transitional cell carcinoma) and T24 (human urinary bladder) tumors were treated with HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a)-PDT alone and in combination with BCG. The HPPH, a multifunctional agent, was selected as a photosensitizer because of its higher tumor avidity, improved fluorescence imaging ability, and limited skin phototoxicity than Photofrin, a current clinical standard. Methods: Imaging: IVIS/Spectrum: A noninvasive in vivo, continuous wave fluorescence imaging apparatus used to assess the localization and distribution of the PS at variable time points. In vivo efficacy studies using UMUC3 and T24 tumors in SCID mice with PS HPPH in combination with BCG. Results: Imaging: Tumor uptake in UMUC3 and T24 tumors using IVIS Imaging. PS HPPH showed high tumor uptake and significant difference in their pharmacokinetic profiles in UMUC3 and T24 tumors implanted in SCID mice: The SCID mice bearing either UMUC3 or T24 tumors (4-5 mm size) were injected with the PS HPPH. The tumored mice (3 mice/group) at a dose of 0.47 u-mol/kg) and imaged at variable time points. The uptake of tumor, liver, and skin was measured by IVIS system and interesting pharmacokinetic profiles of the PS were observed. The optimal tumors uptake in UMUC3 and T24 were at 24 hours and 8-12 hours, respectively. In vivo efficacy studies: PS (HPPH) in combination with BCG shows enhanced PDT efficacy CR (Cures) Day 30 = 14/22 = 63.6% and RG (Re-Growth) 6/22 = 36.4% in bladder tumors (UMUC3). To investigate the utility of combination treatment approach for treating bladder cancer, mice bearing UMUC3 tumors were injected intravenously with HPPH (0.47 u-mol/kg) and the tumors were exposed to laser light (135 J/cm2, 75 mW/cm2) at 24 h post-injection. One hour after the PDT treatment, BCG was injected (1-1.5 × 106 CFU), SQ weekly x 3 doses, and at day 30 the results are very encouraging. Conclusions: The HPPH showed higher in vivo uptake (determined by fluorescence) in UMUC3 and T24 bladder cancer tumors with significant differences in the two tumor types. The treatment of HPPH-PDT in combination with BCG using SCID mice bearing UMUC3 tumors showed enhanced long-term tumor cure. Before initiating this approach to human phase I clinical trial, further studies are under way. Source of funding: Roswell Park Alliance Foundation. Citation Format: Farukh Durrani, Ahmed Aly, Khurshid Guru, Ravindra Pandey. Photodynamic therapy in combination with immunotherapy enhances the long-term cure of bladder cancer in tumored mice [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A02.

Near-Infrared Light-Initiated Upconversion Nanoplatform with Tumor Microenvironment Responsiveness for Improved Photodynamic Therapy.

Photodynamic therapy (PDT) is inflowing the mainstream of the cancer treatments, yet the shallow light penetration, thermal damage to normal cells, poor tumor targeting, and skin phototoxicity compromised the PDT efficacy. This paper designed and prepared an upconversion nanoplatform that could effectively convert 808 nm NIR light to red and green light emission, both of which could excite photosensitizers and exert the PDT curative effects. A thin layer of mesoporous silica covering core-shell nanostructure NaGdF4:Yb,Er@NaGdF4:Yb,Nd upconversion nanoparticles was prepared as the carrier to load the photosensitizer pyropheophorbide-a (PPa), which could be excited by green and red light simultaneously and produce high singlet oxygen (1O2) quantum yield (79.1%). Meanwhile, the chemotherapy drug doxorubicin (DOX) was absorbed in the pores of the SiO2 layer to improve the therapeutic effect, and the folic acid-coupled chitosan (Cs-FA) was modified on the surface of the SiO2 layer to obtain the targeting and biocompatible UCNP@SiO2/PPa&DOX@Cs-FA nanoplatform. The physically adsorbed DOX in the pore channel could be released slowly under faintly acidic or GSH stimuli (84% release of DOX after 16 h), suggesting that the nanoplatform was responsive to the tumor microenvironment. In vitro experiments showed that the combined treatment of PDT and DOX was superior to that of PDT alone or DOX chemotherapy alone, implying a synergistic therapeutic effect. The morphological changes and dye staining research of HeLa cells were consistent with the MTT assay. Therefore, this research provided a strategy for the development of an efficient and safe multifunctional cancer treatment nanoplatform integrating low-intensity light excitation, slow release, targeting, photodynamic therapy, and chemotherapy.

Improved photodynamic anticancer activity and mechanisms of a promising zinc(II) phthalocyanine-quinoline conjugate photosensitizer in vitro and in vivo.

Since the discovery of photodynamic therapy, scientists have constantly been searching for more effective and ideal photosensitizers (PSs). As part of our ongoing interest in the development of more potent photosensitizers, quinoline-8-yloxy-substituted zinc(II) phthalocyanine (ZnPc-Q1) has been identified as a promising photosensitizers in tumor cells. This study aims to explore the photodynamic mechanism and in vivo photodynamic efficacy of ZnPc-Q1, and further evaluate its potential in clinical photodynamic therapy application. The single crystal structure of ZnPc-Q1 enables the easy control of clinical quality standards. In comparison with Photofrin, ZnPc-Q1 exhibits considerably higher in vitro anticancer activity by dual dose-related mechanisms (antiproliferative and apoptosis). In addition, the in vivo results demonstrate that ZnPc-Q1 exhibits significant tumor regression with less skin photosensitivity by both direct killing and apoptosis anticancer mechanisms. In conclusion, ZnPc-Q1 can be considered to be a promising ideal PS for clinical application owing to its defined chemical structure without phthalocyanine isomerization, good absorption of tissue-penetrating red light, improved photodynamic therapy efficacy, and reduced skin phototoxicity.

Photodynamic Therapy Using Talaporfin Sodium for Local Failure after Chemoradiotherapy or Radiotherapy for Esophageal Cancer: A Single Center Experience.

A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice. This study aimed to confirm the efficacy and safety of salvage PDT using talaporfin sodium for esophageal cancer in various clinical situations. Twelve patients with esophageal cancer with local failure after definitive CRT or RT who underwent PDT using talaporfin sodium were enrolled from April 2016 to January 2020. Overall, 10 patients (83.3%) achieved a local complete response. No skin phototoxicity was observed, but esophageal stricture occurred in five patients (41.7%). Esophageal stricture was improved with endoscopic balloon dilation in all patients, and subsequent analysis found no significant factors causing esophageal stricture after PDT. Two patients with synchronous tumors were successfully rescued by combination therapy with endoscopic submucosal dissection. Two patients with carcinoma in situ of larger than 1/2 circumference were rescued by repeated PDT. The 2-year overall survival was 80.0% (95% confidence interval 0.409–0.946). PDT using talaporfin sodium was an effective and safe salvage treatment for esophageal cancer with local failure after CRT or RT in various clinical situations.

5-Aminolevulinic acid patch (Alacare) photodynamic therapy for actinic cheilitis: data from a prospective 12-month follow-up study on 21 patients.

BackgroundActinic cheilitis (AC) is a variant of actinic keratosis (AK) affecting the lips and caused by chronic ultraviolet exposure.ObjectiveAlacare is a self‐adhesive, skin‐coloured 5‐aminolaevulinic acid patch that has been developed for use in photodynamic therapy (PDT) of mild‐to‐moderate AK. Based on promising preliminary results in the treatment of AC with Alacare patch PDT, we decided to extend our previous investigation to gain more data on the efficacy, tolerability, safety and cosmetic outcome of Alacare patch PDT for AC.MethodsTwenty‐one patients with a clinical diagnosis of mild‐to‐moderate AC were included in the study and subjected to one single session of PDT. After occlusion with the Alacare patch for 4 h, the AC lesions were illuminated for 10 min with red light at a dose of 37 J/cm2. All patients received local anaesthesia prior to illumination. Additionally, all lesions were cooled during PDT with a cold air blower. PDT‐induced pain and skin phototoxicity were monitored during and up to 7 days after PDT. Clinical assessment of efficacy, cosmetic outcome and global patient satisfaction was performed at 3, 6 and 12 months after treatment.ResultsNineteen patients completed the study. Three months after PDT, 17 patients (89.5%) had achieved complete remission. Of these, one patient presented with recurrence of AC at the 6‐month follow‐up, whereas all other patients remained in remission until the end of the observation period. The complete clinical cure rate at 1 year after a single Alacare patch PDT thus was 84.2%. Pain during illumination and the phototoxic skin reaction were in general mild to moderate. The cosmetic outcome was excellent.ConclusionThe present prospective study on Alacare patch PDT for AC confirms its high clinical efficacy, good tolerability and favourable cosmetic effects. Alacare patch PDT should be considered as a valid treatment option for patients with AC.

Study of general toxic effect of bacteriosens in rodents and large laboratory animals

Purpose of the study . The objectives of the research are to evaluate the potential toxicity of Bacteriosens when administered to animals once only («acute» toxicity) or repeatedly («chronic» toxicity) and to study its biocompatibility with blood components. Materials and methods . Bacteriosens is the medicine on the basis of photoactive compound of mezo -tetra (3-pyridyl) bacteriochlorin with λ max of 747 nm. Ex vivo study of its biocompatibility with blood components included the evaluation of the impact of the solution on the coagulability of non-stabilized venous blood. The in vitro method of detecting erythrocyte osmotic resistance to hemolytic ability of Bacteriosens was used. The «acute» toxicity was studied in F 1 hybrid mice (CBA x C57Bl/ 6j ) and non-bred rats, male and female, after single intravenous and intraperitoneal injections of Bacteriosens. The «chronic» toxicity was studied in non-bred rats, male and female, and Soviet Chinchilla rabbits after multiple intravenous injection of the drug (over the period of 14 days). Time period before toxicity-induced death of animals, clinical signs of intoxication, and the impact of the medicine on the inner organs and body systems were evaluated using physiologic and pathophysiologic, clinical, and laboratory methods. Results . Incompatibility of non-stabilized rat blood with Bacteriosens after the incubation with the medicine in concentrations varying from 0.5 till 0.005 mg/ml has not been discovered. The aquatic solution of Bacteriosens should be injected into animals and later on into humans slowly or by drip feed in concentrations not exceeding 0.5 mg/ml. A single injection of Bacteriosens in doses from 5.0 to 50.0 mg/kg and from 1.3 to 20.8 mg/kg to mice and rats (male and female), respectively, was tolerated by the animals satisfactorily. No toxicity-induced deaths or skin phototoxicity have been detected. The studied doses of Bacteriosens in mice 25-250 times exceeded the calculated equitherapeutic dose for humans, and in rats, 6.5-104 times. Bacteriosens in total doses from 18.2 to 72.8 mg/kg and from 8.3 to 33 mg/kg administered as multiple intravenous injections for 14 days to rats and rabbits respectively, did not induce the death of the animals and demonstrated no toxic impact on blood, liver, kidneys, heart, hemostasis system, or central nervous system. The drug did not adversely affect carbohydrate and lipid metabolism. Conclusion . Bacteriosens when administered as a single dose or as multiple injections in the range of studied doses did not have adverse toxic effect on mice, rats, and rabbits. The studied doses of Bacteriosens in rats 91-364 times exceeded the calculated equitherapeutic dose for humans, and 41-165 times, in rabbits.