Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

BackgroundPhotodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer (CRC). This review aims to give a general overview of preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment to emphasize their potential in study of PDT mechanism, safety and efficiency to translate these results into clinical benefit in CRC treatment.Materials and methodLiterature on in vitro preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment with the fallowing medical subject headings search terms: colorectal cancer, photodynamic therapy, photosensitizer(s), in vitro, cell culture(s), in vivo, animal experiment(s). The articles were selected by their relevance to the topic.ResultsThe majority of preclinical studies concerning possibility of PDT application in colon and rectal cancer is focused on phototoxic action of photosensitizers toward cultured colorectal tumor cells in vitro. The purposes of animal experiments are usually elucidation of mechanisms of observed photodynamic effects in scale of organism, estimation of PDT safety and efficiency and translation of these results into clinical benefit.Concluding remarksIn vitro photodynamic studies and animal experiments can be useful for studies of mechanisms and efficiency of photodynamic method as a start point on PDT clinical research. The primary disadvantage of in vitro experiments is a risk of over-interpretation of their results during extrapolation to the entire CRC.     

Investigation of cell death mechanisms in human lymphatic endothelial cells undergoing photodynamic therapy

BackgroundPhotodynamic therapy (PDT) has been shown to induce ablation and functional occlusion of tumor-associated lymphatic vessels. However, direct effects of PDT on lymphatic endothelial cells (LECs) have not been studied so far. The aim of this study was to elucidate molecular mechanisms of cell death induced by PDT in human LECs.MethodsVerteporfin was used as a photosensitizer to investigate PDT-mediated damage of lymphatic vessels in mice using immunofluorescent staining and stereomicroscopy. In vitro dose-response studies were carried-out with crystal violet staining. Immunofluorescence, flow cytometry, immunoblotting and DNA electrophoresis were used to investigate the mechanisms of cell death in human LECs undergoing PDT.ResultsPDT induced an increase in the number of propidium iodide positive lymphatic endothelial cells in the mouse dermis. In in vitro studies dose-dependent cytotoxic effects of PDT towards LECs were observed. Typical hallmarks of apoptotic cell death, including Annexin V binding, loss of mitochondrial membrane potential, caspase activation, cleavage of PARP as well as DNA fragmentation were observed in LECs when PDT was used at high irradiation conditions, causing >80% cell death. At lower light fluencies causing <50% cell death PDT induced autophagy rather than apoptosis, as revealed by conversion of LC3-I to the autophagosomal LC3-II and formation of LC3 puncta. Z-VAD-FMK, a caspase inhibitor, prevented cell death induced by high-dose PDT only, while 3-methyladenine, an autophagy suppressor, inhibited cell death induced by low-dose PDT.ConclusionsBoth apoptosis and autophagy are involved in cell death induced by verteporfin-PDT in LECs.     

Effects of ALA-PDT on the macrophages in wound healing and its related mechanisms in vivo and in vitro

BackgroundSeveral studies have suggested the effectiveness of photodynamic therapy (PDT) for wound healing. Macrophages are critical immune cells necessary for regulated inflammation during wound repair. However, the available information regarding the effects of PDT on macrophages during cutaneous wound healing remains insufficient. This study aimed to further investigate these aspects in vivo and in vitro.MethodsMouse full-thickness wound models were used as the study samples to investigate the therapeutic effects and mechanisms of 5-aminolevulinic acid (ALA) PDT. Wound healing rate, granulation tissue formation, local inflammation, M1/M2 macrophages differentiation, were measured at different time points treated by ALA-PDT. The polarization of macrophages induced by ALA-PDT was further evaluated in vitro using PCR and western blot analysis.ResultsALA-PDT could promote formation of granulation tissue, increase inflammatory infiltration and activate M1 macrophages in the early stage of injury. While, ALA-PDT could also facilitate absorption of granulation tissue, inhibit inflammatory infiltration and enhance M2 macrophages polarization in the later stage of wound repair. In vitro, ALA-PDT could modulate the ratio of M2 polarization to M1 polarization via NF-κB signaling pathway.ConclusionsALA-PDT topical application stimulates wound healing by regulating formation of granulation tissue, inflammatory process and M1/M2 macrophages differentiation. The study places a preliminary theoretical basis for topical ALA-PDT to be administered clinically in cutaneous wounds healing.     

Photodynamic therapy for oral potentially malignant disorders: A systematic review and meta-analysis

ObjectivesTo evaluate the effectiveness of Photodynamic Therapy (PDT) in the treatment of Oral Potentially Malignant Disorders (OPMDs) patients.MethodologyAn electronic search was conducted to retrieve articles published until September 2021. Meta-analyses were conducted for the outcomes of complete response (CR) and any response (AR) after treatment with PDT using data from single-arm studies, case series and non-randomised controlled trials (NRCTs).ResultsIn total, 49 articles were included. RCTs revealed insignificant mean difference (MD) in efficacy index between PDT and comparison groups (MD: 1.32; 95% CI:-28.10–30.72, p=0.930). The likelihood of CR (OR:0.84; 95% CI: 0.42–1.71, p=0.637) or AR (OR:2.10; 95% CI: 0.31–14.25, p=0.448) was not different in PDT group when compared with any comparison treatments in NRCTs. CR/AR among single arm studies was 60.6% (95% CI: 50.5–70.7, P<0.001) and 93.7% (95% CI:91.5–95.8, P<0.001) respectively. Higher prevalence of CR and AR was observed for dysplasia or carcinoma insitu (CIS) (CR: 81%, 95% CI: 70.8–91.3, P<0.001; AR: 94.3%; 95% CI: 89–99.6, P<0.001) and actinic cheilitis (AC) (CR: 73.9%, 95% CI: 65.9–81.9, P<0.001; AR:97%; 95% CI:94.9–99, P<0.001).ConclusionsMore than half of the patients receiving PDT showed CR, with more than 90% responding to the treatment. PDT was most effective on oral dysplasias, followed by AC.     

Photodynamic therapy using a cytotoxic photosensitizer porphyrus envelope that targets the cell membrane

BackgroundSubcellular localization of a photosensitizer is known to determine the therapeutic efficacy of photodynamic therapy (PDT). Cell membrane is an optimal target that promises an effective treatment outcome.ObjectivesWe previously developed a novel photosensitizer named porphyrus envelope (PE) by combining hemagglutinating virus of Japan envelope (HVJ-E) with lipidated protoporphyrin IX (PpIX lipid). In the current study, the cellular localization of PE and its ability to induce multiple anti-tumor effect were characterized.Materials and MethodsThe localization and uptake of PpIX lipid in cells were evaluated with confocal laser scanning microscopy and a cell-based fluorescent assay, respectively. The ability of PE to suppress the migration and proliferation of cancer cells was assessed using a scratch-wound assay. The synergistic effect of PDT and HVJ-E treatment was evaluated using an in vitro experiment with PC-3 cells.ResultsPE localized along the cell membrane and PpIX lipid accumulated selectively in the prostate cancer cells within 10 min. Also, PE maintained the ability to undergo fusion and induce cancer cell death even after light irradiation at the dose for PDT. Incubation with PE resulted in delayed migratory and proliferative activity of PC-3 cells. PE-mediated PDT was twice as effective when cells were further incubated with PE following PDT.ConclusionsPE allows rapid drug delivery targeting the cell membrane. Because the cytotoxicity of HVJ-E was maintained, synergistic effect of HVJ-E and the photochemical reactions resulted in highly effective killing of prostate cancer cells in vitro and thus represents a promising treatment for prostate cancer.     

Chitosan-based mucoadhesive gel for oral mucosal toluidine blue O delivery: The influence of a non-ionic surfactant

Photodynamic therapy (PDT) has been successfully employed in the treatment of oral cancer. Toluidine blue O (TBO) is a photosensitizer (PS) that has exhibited remarkable photocytotoxicity in a variety of tumour cells; however, its physicochemical properties, as well as the physicochemical properties of oral mucosa, prevent the drug from reaching the target site at a therapeutic concentration.The aim of this study was to evaluate the influence of Tween 80^® (TW), which has shown potential as a penetration enhancer, on the mucosal retention of TBO for the PDT of oral cancer. 4% Chitosan-based mucoadhesive gels (CH gels) containing or not 5%TW were prepared (both containing 1%TBO), and their physicochemical properties (pH, rheology and mucoadhesion), TBO in vitro release profiles and TBO in vitro mucosal retention were evaluated. In vivo mucosal penetration studies of TBO followed by laser exposition were also carried out.The results showed that 4%CH gels containing 5%TW and 1%TBO have adequate mucoadhesive and rheological properties for oral mucosa use, although they present a slightly acid pH. TBO release studies showed that TW reduces TBO release, but it prolongs TBO release and increases TBO retention in the mucosa. In vivo studies showed that 4%CH gels containing 5%TW and 1%TBO cause an increase in the number of apoptotic cell, after laser exposition.In summary, 4%CH gels containing 5%TW may be a promising vehicle to optimize the penetration of TBO in oral mucosa and to improve the PDT response for the treatment of oral cancer.     

Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma

BackgroundPhotodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor.ObjectiveTo assess methylene blue (MB) as a PDT agent for the treatment of respiratory tract cancer in animal models.MethodsMB-induced PDT was performed on 7 subcutaneous NCI-H460 lung adenocarcinoma xenografts in nude mice and 9 induced squamous cell cancer in the hamster cheek pouch model. In mice, PDT was carried out on right-sided tumors after intratumoral injection of methylene blue 1% (w/v) and illumination at 630 nm at 200 J/cm (Diomed PDT 630), with the left tumor used as control (illumination alone or MB alone). The tumoral volume was assessed before and 15 days after PDT.ResultsFourteen xenografts were treated in mice, including seven treated with MB-PDT, producing a 52% mean tumor volume regression (1568 mm³ vs. 544 mm³) compared to seven control cases in which tumor volume increased (p = 0.007; Mann-Whitney test). Nine cheek pouch induced carcinomas were treated in the hamster group, with a mean volume decrease of 85.8% (from 44.8% to 100%) (initial mean volume = 210 mm³ vs. post PDT mean volume = 97 mm³). Histology analysis showed 4/9 complete responses.ConclusionIntratumoral MB appears efficient as PDT agent for cancer treatment in animal models. Further studies are needed to assess the safety and efficacy of MB-associated PDT for the treatment of lung cancer in humans.     

CuS nanoagents for photodynamic and photothermal therapies: Phenomena and possible mechanisms

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been emerging as attractive and promising methods for tumor treatment in clinical approaches. CuS nanoparticles are effective and cost-effective agents for PTT. Recently, it was observed that CuS nanoparticles are also excellence candidates for PDT. However, the mechanisms for CuS nanoparticles as PDT agents have never been discussed. The goal here is to explore the killing mechanisms of CuS nanoparticles as PTT and PDT agents. CuS nanoparticles were synthesized by a simple wet chemistry method by coating with amphiphilic polymer and examined for their therapeutic potential on lung adenocarcinoma cell line SPC-A-1 in vitro and in vivo using a murine cancer model. The CuS nanoparticles produce heat as well as reactive oxygen species (ROS) when excited by 808 nm laser and show strong anticancer effects both in vitro and in vivo. The heating effects and release of copper ions from CuS upon heating in the tumor acidic environments are the main mechanisms for the generation of reactive oxygen species which are lethal bullets for cancer destruction. As a dual-function agent for PTT and PDT, CuS nanoparticles are promising phototherapy agents for cancer treatment.     

Benefits and safety of photodynamic therapy in patients with hilar cholangiocarcinoma: A meta-analysis

BackgroundPhotodynamic therapy (PDT) is a therapy evaluated for the treatment of cancers resistant to standard oncological treatments. PDT might be beneficial for the palliation of hilar cholangiocarcinoma.AimTo evaluate the efficacy and safety of PDT for treating hilar cholangiocarcinoma.MethodsPubMed, Embase, the Cochrane Library, and Web of Science were searched for articles published up to May 2021. The patients were grouped as PDT+stent vs. stent alone. The outcomes were survival, quality of life, and adverse events (AEs). Data were summarized using hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs).ResultsSix studies were included in this meta-analysis. There were 235 and 211 patients in the PDT+stent and stent groups, respectively. The 1-year survival rate of the PDT+stent group was 0.56, and that of the control group was 0.25. The 2-year survival rate of the PDT+stent group was 0.16, and that of the control group was 0.07. PDT significantly prolonged overall survival compared to the controls (P = 0.002). No differences were detected in the occurrence of cholangitis (P = 0.996) and all other AEs (early complications, stent malfunction, total AEs, acute pancreatitis, liver abscess, and biliary hemorrhage) between the two groups.ConclusionPDT in patients with hilar cholangiocarcinoma could improve survival without additional AEs. Large-scale randomized controlled trials are needed to confirm the findings.     

Antiviral photodynamic therapy: Inactivation and inhibition of SARS-CoV-2 in vitro using methylene blue and Radachlorin

IntroductionRecently, the COVID-19 pandemic has spread globally, necessitating the development of new methods for its prevention and treatment. The purpose of this study was to evaluate the antiviral activity of photodynamic therapy (PDT) against SARS-CoV-2 in vitro.MethodsVero E6 cells and SARS-CoV-2 isolated in Russia were used for PDT with methylene blue (MB) and Radachlorin. A continuous laser with wavelength λ = 662 nm in doses of 16 J/cm² and 40 J/cm² laser irradiation was used for PDT of a viral suspension and SARS-CoV-2-infected cells. The direct cytopathogenic effect of SARS-CoV-2 was evaluated via light microscopy to calculate the TCID₅₀ in the samples and perform statistical analysis.ResultsViral suspensions of SARS-CoV-2 that had a TCID₅₀ greater than 10³ were inactivated by PDT in the presence of MB and Radachlorin. Vero E6 cells were protected from 10⁴ TCID₅₀ of SARS-CoV-2 by PDT post infection. The range of protective concentrations was 1.0–10.0 μg/ml and 0.5–5.0 μg/ml for MB and Radachlorin, respectively. Additionally, it was found that MB and Radachlorin also possess significant antiviral activity even without PDT. The 50 % inhibitory concentration (IC₅₀) against 10² TCID₅₀ of SARS-CoV-2 was found to be 0.22 and 0.33 μg/mL with the addition of MB and Radachlorin, respectively, to cells concomitantly with virus, whereas in the case of applying the photosensitizers at 3.5 h post infection, the IC₅₀ was 0.6 and 2.0 μg/mL for MB and Radachlorin, respectively.ConclusionPDT shows high antiviral activity against SARS-CoV-2 when combined with MB and Radachlorin in vitro.     

Photodynamic therapy for treating infected skin wounds: A systematic review and meta-analysis from randomized clinical trials

BackgroundInfected skin wounds represent a public health problem that effects 20 million people worldwide. Photodynamic therapy (PDT) is a treatment option with excellent results against several infections.ObjectiveThis study aimed to perform a systematic review and meta-analysis on PDT efficacy for treating infected wounds based on randomized clinical trials (RCTs).MethodsPubMed, Scopus, Web of Science, SciELO, and the Cochrane library were searched. The Delphi List criteria and the Revised Cochrane risk-of-bias (Rob 2) were used for evaluating the quality of clinical trials. Meta-analyses were performed with the random-effect model. The odds ratio was the effect measure for binary outcomes, while the standard mean difference was used for continuous outcomes. The trim-and-fill method was used to detect small-study effects. The quality of evidence was verified for each outcome.ResultsOnly four out of 573 articles were selected for the qualitative and quantitative analyses. The most frequent cause of infected wounds was impaired venous circulation (75%). All studies used red LED light. PDT reduced healing time and improved the healing process and wound oxygenation. Patients treated with PDT showed 15% to 17% (p = 0.0003/ I²=0%) lower microbial cell viability in the wound and a significantly smaller wound size (0.72 cm²/p = 0.0187/I²=0%) than patients treated with placebo or red-light exposure. There was a high level of evidence for each meta-analysis outcome.ConclusionPDT can be an excellent alternative treatment for infected skin wounds, though larger trials are needed.     

(18)F]desmethoxyfallypride as a novel PET radiotracer for quantitative in vivo dopamine D2/D3 receptor imaging in rat models of neurodegenerative diseases

Introduction[¹⁸F]desmethoxyfallypride ([¹⁸F]DMFP) is a promising tracer for longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by positron emission tomography (PET) in small animal models. We explored the feasibility of [¹⁸F]DMFP-PET to image D2R availability in rat models of Huntington's (HD) and Parkinson's disease (PD).MethodsAnimals received either unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle injections of 6-OHDA to produce the loss of striatal projection neurones or deplete the striatal dopamine, corresponding to established animal models for HD and PD, respectively. Three weeks after lesioning, PET scans were acquired on a microPET Focus 120 system following the tail vein injection of [¹⁸F]DMFP.Results[¹⁸F]DMFP-PET clearly visualized lesion induced decreases and increases of D2R availability. In vivo estimates of D2R binding and changes thereof gained by pharmacokinetic analyses correlated significantly with D2R density and its change provided by in vitro [³H]raclopride-autoradiography.ConclusionsIn conclusion, [¹⁸F]DMFP-PET is a suitable method for in vivo D2R-assessment in preclinical research, e.g for monitoring cell-based therapies.     

Combined RNA interference of adenine nucleotide translocase-2 and ganciclovir therapy in hepatocellular carcinoma

PurposeThe purpose of this study was to investigate the anticancer effects of combined RNA interference (RNAi) of the adenine nucleotide translocase-2 (ANT2) gene and ganciclovir (GCV) therapy for treatment of hepatocellular carcinoma cells (Huh 7) in an animal model.MethodsThe Huh 7/NTG stable cell line was established by transfection of a vector with the human sodium iodide symporter (hNIS), HSV1-sr39 thymidine kinase (tk), and enhanced green florescent protein (EGFP) fusion gene into Huh 7 cells. mRNA expressions of these genes were evaluated by RT-PCR analysis. The functions of hNIS and HSV1-sr39tk were verified with ¹²⁵I uptake and ³H-penciclovir (PCV) uptake tests. EGFP and hNIS expression was confirmed with confocal microscopy after immunocytochemical staining. We treated the tumor cells with ANT2 shRNA or GCV or both ANT2 shRNA and GCV and treated the in vivo mouse model with a Huh 7/NTG tumor xenograft. The therapeutic effects of the in vivo study were assessed with caliper measurements and gamma camera imaging using ^99mTc-pertechnetate.ResultsHuh 7/NTG cells showed a cell number-dependent increase in ¹²⁵I uptake and a 24-fold higher ³H-PCV uptake compared to parent Huh 7 cells. Huh 7/NTG cells transfected with ANT2 shRNA had lower ANT2 mRNA expression and more impaired proliferation activity than cells transfected with scramble shRNA. Proliferation of Huh 7/NTG cells was also inhibited by GCV treatment. Combined GCV and ANT2 shRNA therapy further inhibited cell proliferation in the in vitro study. The combined therapy with GCV and ANT2 shRNA showed a further decrease in tumor growth in the mouse model.ConclusionsOur results suggest that the combined RNA interference with ANT2 and GCV therapy inhibited hepatocellular carcinoma cell proliferation more than single GCV therapy or ANT2 shRNA therapy in vitro and in vivo. Therefore it could be applied treating incurable hepatocellular carcinoma.     

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study

BackgroundPhotodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma.MethodsAn MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660 nm) at different power densities (1.25–180 J/cm²), the photosensitizer methylene blue (MB) at concentrations of 0.39–100 μM, PDT (12.5 μM MB and laser power densities from 1.25 to 180 J/cm²), and PDT (12.5 μM MB and a laser density of 120 J/cm²) plus ERL (1 μM).ResultsThe laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone.ConclusionsThe sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.     

Photodynamic therapy in oral potentially malignant disorders—Critical literature review of existing protocols

IntroductionOral cancer is a serious public health issue. Apart from its high rate of prevalence, incidence and mortality, it can often result in more complex and expensive treatment when diagnosed late. Potentially malignant disorders (PMDs) can precede oral cancer, and are usually treated by surgical excision. However, in many cases patients are elderly and multiple interventions may be required. Photodynamic therapy (PDT) is a simple alternative, which has been successfully used in the treatment of oral PMDs.ObjectiveDue to the lack of standardization regarding photosensitizers (PTSs), types of irradiation, and methods of application, the objective of this study was to analyze existing PDT protocols in an attempt to identify the one that demonstrates greater efficiency, reliability and feasibility in the treatment of oral PMDs for both researchers and clinicians.MethodsOriginal clinical studies published only in English between 1993 and 2016 were searched in Pubmed/Medline database using the following keywords: photodynamic therapy; oral potentially malignant disorder; oral premalignant lesions. Review articles; experimental studies; case-reports; commentaries; and letters to the Editor were excluded from the selection.Results and conclusionBased on the 16 studies selected, the topical 5-ALA-20% PTS, associated to a LED light applied for 15 min with a 7-day interval between sessions emerged as the most frequently used PDT protocol, with satisfactory results. Due to its low rate of side effects, this PDT protocol presents good potential for the treatment of oral PMDs. Further clinical studies are required to ascertain its long-term validity in preventing oral cancer.     

Photosensitizer Delivery with Functional Polymers Exerting pH-Responsive Isothermal Phase Transition

Photosensitizer delivery is prerequisite for successful photodynamic therapy (PDT), and many photosensitizers have been developed and investigated in in vitro and in vivo studies [1]. In general, hydrophobic photosensitizers can efficiently interact with biological components including cell membrane via hydrophobic interaction and exhibit high cellular uptake, inducing strong PDT effects in in vitro conditions.However, in in vivo conditions, such hydrophobic photosensitizers also interact with normal cells and tissues as well as target tumours, which causes unfavourable photochemical damage. On the other hand, hydrophilic photosensitizers avoid unfavourable interaction with biological components and their retention in the skin, reducing photosensitivity which is one of the side effects in PDT. However, the compromised interaction leads to low cellular uptake and PDT effects. Thus, it is difficult to develop photosensitizers that can induce strong PDT effects without showing severe photochemical damage to normal tissues.In this study, to integrate these conflicting properties of hydrophobic/hydrophilic photosensitizers, we developed a functional polymer exerting isothermal hydrophilic-to-hydrophobic phase transition in response to mildly acidic pH in tumours [2]. The backbone of the polymer was a poly(N-isopropylacrylamide) derivative, which is well known to show lower critical solution temperature, and its side chain was modified with hydrophilic pH-cleavable moieties. The polymer termed P(NIPAAm/AIPAAm-PMM) showed hydrophilicity in a physiological condition (37°C, pH 7.4); however, in a tumour microenvironment-like condition (37°C, pH ≤ 6.9), P(NIPAAm/AIPAAm-PMM) exhibited hydrophobicity by detaching the hydrophilic moieties from the side chain. Owing to this pH-responsive hydrophilic-to-hydrophobic phase transition, the polymer exerted efficient cellular uptake in a pH-responsive manner. We then conjugated a phthalocyanine-based photosensitizer (IRDye 700DX) with the polymer and examined the potential of the polymer for PDT. In in vitro study, The photosensitizer-polymer conjugate exhibited strong PDT effects at acidic pH because of the aforementioned pH-responsive cellular uptake. In in vivo study, the photosensitizerpolymer conjugate efficiently accumulated within tumours in mice after intravenous injection and accomplished significantly enhanced PDT effects. Our results indicate that the control of hydrophilicity and hydrophobicity may be a promising approach to develop new photosensitizers for successful PDT.     

Antifungal effect of a new photosensitizer derived from BODIPY on Candida albicans biofilms

BackgroundPhotodynamic therapy (PDT) may be an alternative treatment of Candida albicans (C. albicans) infections. The aim of this study was to investigate the antifungal effect of PDT mediated by a new photosensitizer (PS) derived from BODIPY (BDP-4L) on C. albicans biofilms.MethodsC. albicans biofilms were incubated with BDP-4L of different concentrations and then irradiated at the light doses of 1.8, 3.6, 5.4, 7.2 and 9.0 J/cm². XTT reduction assay was conducted to determine the PS concentration and PDT parameters. Confocal light scanning microscopy (CLSM) and scanning electron microscope (SEM) were used to visualize and quantify the effect of BDP-4L on C. albicans biofilms after PDT.ResultsC. albicans biofilms were inactivated in light dose-dependent and PS concentration-dependent manners using BDP-4L as PS. Without irradiation, no inactivation effect was observed when PS concentrations varied from 5 μM to 80 μM. 40 μM PS with 3.6 J/cm² irradiation resulted in a significant reduction of 83.8% in biofilm metabolic activities. CLSM assay demonstrated that cell viability was obviously inhibited by 82.6%. SEM images revealed ruptured and rough cell surface, indicating increased cell membrane permeability after PDT.ConclusionsOur results suggested that BDP-4L mediated PDT exhibited a favorable antifungal effect on C. albicans biofilms.     

Retrospective analysis of therapeutic effect and prognostic factors on early glottic carcinoma

ObjectiveTo investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors.MethodsRetrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n = 152), radiotherapy (n = 20) and PDT (n = 30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of χ ²test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data.ResultsThere was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group.ConclusionsThe therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tis ∼ T₂N₀M₀). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear.     

Photodynamic therapy using OR141-loaded nanovesicles for eradication of leukemic cells from ovarian tissue

In 2020, the estimated number of new leukemia cases was higher than 30,000 in girls between 0 and 19 years old. Due to cancer treatment, some of these patients may lose both endocrine and reproductive functions. Transplantation of cryopreserved ovarian tissue is not advised after cancer remission because it has a high risk of reintroducing malignant cells in the patient, potentially leading to leukemia recurrence. To safely transplant the ovarian tissue from these patients and restore their fertility, our goal was to develop a photodynamic therapy (PDT) strategy to eliminate leukemia ex vivo. To this end, we designed, optimized, and characterized OR141-loaded niosomes (ORN) to develop the most effective formulation for ex vivo purging ovarian fragments from chronic myelogenous leukemia cells. After establishing the best ORN formulation, the PDT efficiency of optimized ORN was determined for human ovarian stromal cells and acute myeloid leukemia cell line (HL60). Blank niosomes treatment on ovarian stromal cells causes no significant toxicity, showing that the composition of the nanoparticle is not toxic. On the other hand, the in vitro studies showed that while ovarian stromal cells were still viable (82.04 ± 2.79%) after the treatment by 0.5 µM ORN, the same treatment yielded 95.43 ± 3.89% toxicity and cell death in the cancer cells. In conclusion, our results showed that our novel PDT procedure could be a promising strategy to destroy leukemia cells in ovarian tissue fragments allowing safe transplantation in cancer survivors.