A Self-assembled Nanomicelle for Realizing Tumor Photodynamic Therapy via Increasing Drug Accumulation and Prolonging Retention Time

A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.

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.

Design of a nanozyme-based magnetic nanoplatform to enhance photodynamic therapy and immunotherapy

The tumor microenvironment, particularly the hypoxic property and glutathione (GSH) overexpression, substantially inhibits the efficacy of cancer therapy. In this article, we present the design of a magnetic nanoplatform (MNPT) comprised of a photosensitizer (Ce6) and an iron oxide (Fe3O4)/manganese oxide (MnO2) composite nanozyme. Reactive oxygen species (ROS), such as singlet oxygen (1O2) radicals produced by light irradiation and hydroxyl radicals (·OH) produced by catalysis, are therapeutic species. These therapeutic substances stimulate cell apoptosis by increasing oxidative stress. This apoptosis then triggers the immunological response, which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer. Furthermore, MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed via a non-cyanine dye

The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy(PDT)and photothermal therapy(PTT)under the stimulation of near-infrared(NIR)light(commonly 808 nm).Unfortunately,the stability of NIR-excited cyanine dyes is not satisfactory.These cyanine dyes can be attacked by self-generated reactive oxygen species(ROS)during PDT processes,resulting in structural damage and rapid degradation,which is fatal for phototherapy.To address this issue,a novel non-cyanine dye(IR890)was elaborately designed and synthesized by our team.The maximum absorption wavelength of IR890 was located in the deep NIR region(ca.890 nm),which was beneficial for further improving tissue penetration depth.Importantly,IR890 exhibited good stability when continuously illuminated by deep NIR light.To improve the hydrophilicity and biocompatibility,the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer(POEGMA-b-PGMA-g-C≡CH)via click chemistry.Then,the synthesized POEGMA-b-PGMA-g-IR890 amphiphilic polymerwas utilized to prepare P-IR890 nano-photosensitizer via self-assembly method.Under irradiation with deep NIR light(850 nm,0.5 W/cm^(2),10 min),the dye degradation rate of P-IR890 was less than 5%.However,IR780 was almost completely degraded with the same light output power density and irradiation duration.In addition,P-IR890 could stably generate a large number of ROS and heat at the same time.It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer via irradiation with deep NIR light.P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway.Therefore,the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.

Light/pH dual controlled drug release"nanocontainer"alleviates tumor hypoxia for synergistic enhanced chemotherapy,photodynamic therapy and chemodynamic therapy

Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Alkyl chain length-regulated in situ intelligent nano-assemblies with AIE-active photosensitizers for photodynamic cancer therapy

Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their dependence on oxygen severely limits their application.Aggregation-induced emission(AIE)PSs can dramatically facilitate the photosensitization effect,which can have positive impacts on tumor PDT.To-date,most AIE PSs lack tumor targeting capability and possess poor cell delivery,resulting in their use in large quantities that are harmful to healthy tissues.In this study,a series of AIE PSs based on pyridinium-substituted triphenylamine salts(TTPAs 1-6)with different alkyl chain lengths are synthesized.Results reveal that TTPAs 1-6 promote the generation of type I and II ROS,including·OH and 1O_(2).In particular,the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains.Additionally,they can assemble with albumin,thereby forming nanoparticles(TTPA 4-6 NPs)in situ in blood,which significantly facilitates mitochondrial-targeting and strong ROS generation ability.Moreover,the TTPA 4-6 NPs are pH-responsive,allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect.Therefore,the in vivo distributions of TTPA 4-6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy.This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.

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.

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.

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.

Hydroxyethyl starch conjugates co-assembled nanoparticles promote photodynamic therapy and antitumor immunity by inhibiting antioxidant systems

Photodynamic therapy(PDT)can produce high levels of reactive oxygen species(ROS)to kill tumor cells and induce antitumor immunity.However,intracellular antioxidant systems,including glutathione(GSH)system and thioredoxin(Trx)system,limit the accumulation of ROS,resulting in compromised PDT and insufficient immune stimulation.Herein,we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a(PPa)and cisplatin prodrug Pt-COOH(Ⅳ)(Pt(Ⅳ))based on hydroxyethyl starch(HES)to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses.Specifically,HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt(Ⅳ),and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt(Ⅳ).PtHPs improved PPa photostability while retaining PPa photodynamic properties.In vitro experiments showed that PtHPs reduced GSH,inhibited Trx system and had better cell-killing effect and ROS generation ability.Subcutaneous tumormodels showed that PtHPs had good safety and tumor inhibition effect.Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells,induced T cell-mediated immune responses,and thus suppressed the growth of both primary and distal tumors.This study reports a novel platinum-based nanomedicine and provides a newstrategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.

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.

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.

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.

Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy

Glutathione(GSH)-activated prodrugs are promising for overcoming the limitations of conventional anti-tumor drugs.However,current GSH-responsive disulfide groups exhibit unregulated reactivity,making it impossible to precisely control the drug release rate.We herein report a series of GSH-responsive prodrugs with a“three-in-one”molecular design by integrating a fluorescence report unit,stimuliresponsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution(SNAr)reactivity.The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron-withdrawing or-donating abilities on the BODIPY core.Furthermore,the prodrugs self-assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy(PDT).The PDT process also increases the concentration of GSH in cells,further promoting the release of drugs for chemotherapy.This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.

A self-reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy

As a novel drug development paradigm,selective activation of prodrugs provides the potential for precise tumor chemotherapy,thereby presenting an opportunity for advancing cancer treatment.The combination of photodynamic therapy(PDT)and prodrug can enhance the therapeutic efficacy while simultaneously enabling real-time monitoring of drug distribution and release.However,the tumor hypoxia microenvironment and the frequent high-dose administration of prodrugs signifi-cantly impede therapeutic efficacy and escalate treatment-related risks.Herein,a tumor microenvironment-specific release prodrug is constructed,termed NBS-2S-5FU.Under the influence of glutathione(GSH),NBS-2S-5FU undergoes activa-tion,leading to the release of photosensitizer NBS and chemotherapeutic agent 5-FU derivatives.Under irradiation,NBS produces sufficient superoxide radical(O-•2)while 5-FU derivatives inhibit DNA biosynthesis,thereby effectively sup-pressing tumor growth at low doses.Subsequent in vivo studies utilizing NBS-2S-5FU liposomes exhibit outstanding anti-cancer effectiveness.This study highlights a promising direction for advancing combined prodrugs that integrate PDT and chemotherapy.

Photodynamic therapy promotes hypoxia-activated nitrogen mustard drug release

Photodynamic therapy(PDT)has become a promising method for tumor treatment due to its non-invasive and high spatiotemporal selectivity.However,PDT is still hindered by reactive oxygen species deficiency,because solid tumors feature a hypoxic microenvironment.PDT combined with hypoxia-activated chemotherapy drugs can effectively induce tumor death,overcoming the limitations of the sole PDT for the fight against hypoxia.Herein,we designed a nanosystem(PCe6AZOM)that enhances the release of hypoxia-activated drugs(AZOM)by PDT.Under hypoxic conditions,the azo bond of AZOM is cleaved by azo reductase,releasing highly cytotoxic AZOM and resulting in a significant increase in intratumor drug concentration.Meanwhile,the commercial photosensitizer Ce6 can aggravate the oxygen-poor state during the PDT process and further cause more AZOM release.Moreover,the cascade reactions in the nanosystem could activate singlet oxygen and enhance drug release through 660 nm light laser irradiation,contributing to more effective induction of tumor apoptosis and tumor growth retardation in vitro and in vivo.

Study of Effects of Photodynamic Therapy(PDT),in Scar-Induced Skin Wounds in Rats Wistar:The New Clinical Perspective for Ulcers

Photodynamic therapy today is becoming an important role in the healing of lacerated tissues, since it has therapeutic resources capable of accelerating this process. One treatment option is the clinical phototherapy, and Photodynamic Therapy (PDT) is being widely used. This study aims to evaluate the effect of PDT on the healing of skin wounds in rats. We used a sample of 39 male rats Wistar divided into three groups, a control, a PDT-treated green and red with the last PDT. After 24 hours before the surgical incisions, PDT was used in both groups for 6 minutes and was evaluated in histological level, the inflammatory reaction and the repair process. The results showed that the granulation tissue was more developed in the irradiated group than in the control group and the amount of chronic inflammatory cells (monocytes, macrophages, lymphocytes and plasma cells) predominated with green phototherapy. The epithelialization in the wound margins and scarring with better quality occurred with red PDT (640 nm), which the higher deposition was of collagen. However, phototherapy not collimated of 640 nm (red) resulted in better anti-inflammatory effects. Given these answers with phototherapy not collimated green (525 nm) and red (640 nm), we conclude that the use of these wavelengths is possible with benefits, mainly with red LED.

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.

Recent Advances in Tumor Microenvironment Hydrogen Peroxide-Responsive Materials for Cancer Photodynamic Therapy

Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting tumor cells from damage caused by common treatments.High concentration of hydrogen peroxide(H2O2),one of the hallmarks of TME,has been recognized as a double-edged sword,posing both challenges,and opportunities for cancer therapy.The promising perspectives,strategies,and approaches for enhanced tumor therapies,including PDT,have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine.In this review,we outline the latest advances in H2O2-responsive materials,including organic and inorganic materials for enhanced PDT.Finally,the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.

Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia,it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy.Here we describe a patient with a progressive dysplastic lesion in the common bile duct,which developed from moderate-high to highgrade dysplasia in approximately 2 mo.The patient refused major surgery.Therefore,endoscopic-assisted photodynamic therapy was performed.The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic.This report is the first to describe the successful treatment of highgrade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.