Potential of photodynamic therapy in the management of infectious oral diseases

Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.

Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage‑Based Host–Guest Complexation for Photodynamic Therapy

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET,which will open a new avenue for host–guest chemistry-based supramolecular theranostics.

Tissue optical clearing enhances efficacy of vascular targeted photodynamic therapy of mouse dorsal skin

Vascular-targeted photodynamic therapy(V-PDT)is an effective treatment for port wine stains(PWS).However,repeated treatment is usually needed to achieve optimal treatment outcomes,possibly due to the limited treatment light penetration depth in the PWS lesion.The optical clearing technique can increase light penetration in depth by reducing light scattering.This study aimed to investigate the V-PDT in combination with an optical clearing agent(OCA)for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model.Vascular responses were closely monitored with laser speckle contrast imaging(LSCI),optical coherence tomography angiography,and stereo microscope before,during,and after the treatment.We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature.The combination of OCA and V-PDT resulted in significant vascular damage,including vasoconstriction and the reduction of blood flow.Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases,including PWS.

Reduction of photodynamic damage of blood vessels in the protected region by(–)-epigallocatechin gallate

Photodynamic therapy(PDT)has been increasingly used in the clinical treatment of neoplastic,inflammatory and infectious skin diseases.However,the generation of reactive oxygen species(ROS)may induce undesired side effects in normal tissue surrounding the treatment lesion,which is a big challenge for the clinical application of PDT.To date,(–)-Epigallocatechin gallate(EGCG)has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage.This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether(Hemoporfin)-mediated PDT.The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be 6.8×10^(8)M^(−1)S^(−1),respectively.The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel,suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG.This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2,and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy:Novel insights and perspectives

Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.

Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Photodynamic therapy with TBZPy regulates the PI3K/AKT and endoplasmic reticulum stress-related PERK/eIF2α pathways in HeLa cells

Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.

Advances in photodynamic therapy for port-wine stain and our experience

Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.

Clinical Study of Photodynamic Therapy for Upper Gastrointestinal Tract Cancers

Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.

Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration

AIM:To compare the efficacy of low-fluence photodynamic therapy(PDT) combinations in the treatment of age-related macular degeneration(AMD).· METHODS:Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity(BCVA) was ≥0.3(Snellen) were enrolled.15 patients in Group I underwent low-fluence PDT(25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination,15 patients in Group II underwent PDT(50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while,15 patients in Group III underwent intravitreal pegaptanib monotherapy.Complete ophthalmologic examinations were performed in pre and post treatment visits,and the results were statistically analised.A clinical activity score(CAS) was calculated by using changes in lesion size,amount of hemorrhage,staining pattern in FA and OCT measurement of intra/subretinal fluid.≤3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment.· RESULTS:The mean age of 19 female(42.2%) and 26 male(57.8%) patients was(72.82±8.02) years.Mean follow-up was(13.93±5.87) months.Lesion type was occult in 28 eyes(62.2%).Treatment success rates according to BCVA assessments were 86.7%,80%,60% and mean BCVA decrease were 0.3,1.0,2.2 logMAR lines in Group I,II and III,respectively(P >0.05).According to the changes in central macular thickness and CAS,no difference was found among the study groups(P =0.850 and P =0.811,respectively).Patients treated with combination regimens had lower intravitreal injection frequencies(P =0.015).· CONCLUSION:Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.·

Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis

To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.

Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

Photodynamic therapy vs radiofrequency ablation for Barrett's dysplasia: Efficacy,safety and cost-comparison

AIM:To compare effectiveness,safety,and cost of photodynamic therapy(PDT)and radiofrequency ablation(RFA)in treatment of Barrett’s dysplasia(BD).METHODS:Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared.Thirty-three patients with high-grade dysplasia(HGD)had treatment with porfimer sodium photosensitzer and 630 nm laser(130 J/cm),with maximum of 3 treatment sessions.Fifty-three patients with BD(47 with low-grade dysplasia-LGD,6 with HGD)had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions.Both groups received proton pump inhibitors twice daily.Endoscopic biopsies were acquired at 2 and 12 mo after enrollment,with 4-quadrant biopsies every 1 cm of the original BE extent.A complete histological resolution response of BD(CR-D)was defined as all biopsies at the last endoscopy session negative for BD.Fisher’s exact test was used to assess differences between the two study groups for primary outcomes.For all outcomes,a two-sided P value of less than 0.05 was considered to indicate statistical significance.RESULTS:Thirty(91%)PDT patients and 39(74%)RFA were men(P=0.05).The mean age was 70.7±12.2 and 65.4±12.7(P=0.10)year and mean length of BE was 5.4±3.2 cm and 5.7±3.2 cm(P=0.53)for PDT and RFA patients,respectively.The CR-D was(18/33)54.5%with PDT vs(47/53)88.7%with RFA(P=0.001).One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA.PDT was five times more costly than RFA at our institution.The two groups were not randomized and had different BD grading are the limitations of the study.CONCLUSION:In our experience,RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Single NIR Laser-Activated Multifunctional Nanoparticles for Cascaded Photothermal and Oxygen-Independent Photodynamic Therapy

Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies(PTT and PDT).Herein,Bi2Se3@AIPH nanoparticles(NPs)are facilely developed to overcome these problems.Through a one-step method,free radical generator(AIPH)and phase transition material(lauric acid,LA,44-46°C)are encapsulated in hollow bismuth selenide nanoparticles(Bi2Se3 NPs).Under a single 808-nm laser irradiation at the tumor area,hyperthermia produced by Bi2Se3 not only directly leads to cell death,but also promotes AIPH release by melting LA and triggers free radical generation,which could further eradicate tumor cells in hypoxic environments.Moreover,Bi2Se3 with high X-ray attenuation coefficient endows the NPs with high computed tomography(CT)imaging capability,which is important for treating area determination.The results exhibit that Bi2Se3@AIPH NPs possesses 31.2%photothermal conversion efficiency for enhanced PTT,ideal free radical generation for oxygen-independent PDT,and 37.77 HU mL mg?1 X-ray attenuation coefficient for CT imaging with high quality.Most importantly,the tumor growth inhibition rate by synergistic PTT,PDT,and following immunotherapy is 99.6%,and even one tumor disappears completely,which demonstrates excellent cascaded synergistic effect of Bi2Se3@AIPH NPs for the tumor therapy.

Recent advances in photodynamic diagnosis of gastriccancer using 5-aminolevulinic acid

Photodynamic diagnosis based on 5-aminolevulinic acidinduced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative realtime fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.