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Regression Analysis of Protoporphyrin IX Measurements Obtained During Dermatological Photodynamic Therapy
摘要： Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of dermatological cancers and precancers. Improvement of efficacy is required to widen its application. Clinical protoporphyrin IX (PpIX) fluorescence data were obtained using a pre-validated, non-invasive imaging system during routine methyl aminolevulinate (MAL)-PDT treatment of 172 patients with licensed dermatological indications (37.2% actinic keratosis, 27.3% superficial basal cell carcinoma and 35.5% Bowen’s disease). Linear and logistic regressions were employed to model any relationships between variables that may have affected PpIX accumulation and/or PpIX photobleaching during irradiation and thus clinical outcome at three months. Patient age was found to be associated with lower PpIX accumulation/photobleaching, however only a reduction in PpIX photobleaching appeared to consistently adversely affect treatment efficacy. Clinical clearance was reduced in lesions located on the limbs, hands and feet with lower PpIX accumulation and subsequent photobleaching adversely affecting the outcome achieved. If air cooling pain relief was employed during light irradiation, PpIX photobleaching was lower and this resulted in an approximate three-fold reduction in the likelihood of achieving clinical clearance. PpIX photobleaching during the first treatment was concluded to be an excellent predictor of clinical outcome across all lesion types.
关键词： photobleaching,aminolevulinic acid (ALA; Ameluz),dermatology,protoporphyrin IX (PpIX),imaging,methyl aminolevulinate (MAL; Metvix),photodynamic therapy (PDT),fluorescence,non-melanoma skin cancer (NMSC)
更新于2025-09-23 15:22:29
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Study on Five Porphyrin-Based Photosensitizers for Singlet Oxygen Generation
摘要： Five porphyrin derivatives were synthesized and characterized in order to be utilized as photosensitizers for singlet oxygen generation. UV-Vis absorption properties of porphyrins were experimentally and theoretically discussed. The results indicated that the increase in π-conjugation of porphyrin core can lower the S1-T1 energy gap and is favorable for efficient energy transfer. The singlet oxygen generation ability of porphyrins was measured and compared under both simulated sunlight and yellow light. As for the results using simulated sunlight, EBHPP and CEBHPP exhibited best and similar performance because they bear strong near-IR absorption and S1-T1 interactions. However, under yellow light conditions CEBHPP has better ability for singlet oxygen generation because of strong absorbance from 650–750 nm. The DNA photocleavage measurements were performed to evaluate the biological activity of the porphyrin derivatives. The photocleavage activities were in the order of TPP < TPP-NO2 < BHPP < EBHPP < CEBHPP, and the possible reasons were discussed. This work is useful for the design of more efficient photosensitizers.
关键词： Photosensitizer,Porphyrin,Singlet oxygen,UV-Vis absorption,Photodynamic therapy
更新于2025-09-23 15:22:29
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Hyaluronic Acid-zinc Protoporphyrin Conjugates for Photodynamic Antitumor Therapy
摘要： Zinc (II) protoporphyrin IX (ZnPP) strongly inhibits antioxidative enzyme heme oxygenase-1 (HO-1), and ZnPP generates reactive oxygen species (ROS) upon light irradiation. ZnPP can induce lethal oxidative stress in the tumor, when ZnPP is selectively delivered to the tumor followed by light irradiation. In this study, ZnPP was conjugated to hyaluronic acid (HA-ZnPP) for improving its solubility in aqueous media and tumor selective delivery of ZnPP by the enhanced permeability and retention (EPR) effect. Though photosensitizing activity of the HA-ZnPP was quenched in phosphate buffered saline, it was partially recovered by addition of lecithin. Similar to other polymer-conjugated ZnPP, cellular uptake of the HA-ZnPP was lower than that of the free ZnPP in HeLa cells. In tumor-bearing mice, plasma half-life of HA-ZnPP became longer than that of free ZnPP, and thus selective accumulation of the HA-ZnPP in the tumor by the EPR effect was observed. Combination of the HA-ZnPP and light irradiation potentially suppressed the tumor growth, approximately 60% tumor volume reduction was observed without apparent adverse effects at day 31 after the drug treatment. These data demonstrate that HA is a preferable carrier for ZnPP, and the HA-conjugated ZnPP is a promising antitumor agent for photodynamic therapy.
关键词： Nanomedicine,EPR,Zinc protoporphyrin,Photodynamic therapy,Hyaluronic acid
更新于2025-09-23 15:22:29
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Photomedicine - Advances in Clinical Practice || Light-Emitting Woven Fabric for Treatment with Photodynamic Therapy and Monitoring of Actinic Keratosis
摘要： A successful photodynamic therapy (PDT) requires a specific photosensitizer, oxygen and light of a specific wavelength and power. Today photodynamic therapy (PDT) is administered to patients with light-emitting diode (LED) panels. These panels deliver a non-uniform light distribution on the human body parts, as the complex human anatomy is not a flat surface (head vertex, hand, shoulder, etc.). For an efficient photodynamic therapy (PDT), a light-emitting fabric (LEF) was woven from plastic optical fibers (POF) aiming at the treatment of dermatologic diseases such as actinic keratosis (AK). Plastic optical fibers (POF) (Toray, PGR-FB250) have been woven in textile in order to create macro-bendings, and thus emit out the injected light directly to the skin. The light intensity and light-emitting homogeneity of the LEF were improved thanks to Doehlert Experimental Design. During the treatment with PDT, the photosensitizers were activated in the cancerous cells. These cells may be visualized, as they show a characteristic fluorescence under UV light, which is called fluorescence diagnosis (FD). Therefore, it is proposed to modify the developed LEF for PDT to measure the fluorescence amount. For this aim, a part of POFs was cut out to observe the quantity of light that could be collected while the LEF was connected to a light source. The first prototypes showed the possibility of the illumination with the same LEF without losing the efficiency but also imaging the collected light.
关键词： fluorescence diagnosis (FD),weaving,light emitting fabric (LEF),plastic optical fiber (POF),photodynamic therapy (PDT)
更新于2025-09-23 15:22:29
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Physiologically Stable Hydrophilic C60 Nanoparticles for Photodynamic Therapy
摘要： Hydrophilic C60 nanoparticles that are highly stable in living systems were prepared with sugammadex, an anionic γ-cyclodextrin derivative, via a simple procedure for use in biological applications. The prepared C60/sugammadex nanoparticles showed outstanding stability under physiological conditions and even in much harsher conditions. The sugammadex interacted with C60 nanoparticles through strong host-guest interactions on the particle surface, producing a negatively charged layer on the surface of nanoparticles, which contributed to the high stability of the nanoparticles. In addition, the nanoparticles were highly stable in the presence of singly charged cations which are present in abundance in living systems. The stable C60/sugammadex nanoparticles showed a significantly different biological behavior compared to less stable C60 nanoparticles after intravenous administration. Most of the C60 particles accumulated and remained in organs of the reticuloendothelial system (RES) after administration, which are susceptible to forming aggregates in physiological conditions. On the other hand, the C60/sugammadex nanoparticles showed a completely different biological behavior, i.e. longer blood circulation, low RES uptake and elimination with time from organs. The photodynamic activity of C60/sugammadex nanoparticles was evaluated both in vitro and in vivo, and an outstanding antitumor effect was achieved based on the generation of reactive oxygen species under light irradiation. We envision that such stable C60 nanoparticles would be a desirable approach for extending the biological applications of these materials and the precise evaluation of C60 activity in living systems.
关键词： nanoparticle,biodistribution,in vivo aggregation,photodynamic therapy,fullerene
更新于2025-09-23 15:22:29
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Photoimmunoconjugates: novel synthetic strategies to target and treat cancer by photodynamic therapy
摘要： Photodynamic therapy (PDT) combines a photosensitizer (PS) with the physical energy of non-ionizing light to trigger cell death pathways. PDT has potential as a therapeutic modality to be used in alternative or in combination with other conventional cancer treatment protocols (e.g. surgery, chemotherapy and radiotherapy). Still, due to the lack of specificity of the current PSs to target the tumor cells, several studies have exploited their conjugation with targeting moieties. PSs conjugated with antibodies (Abs) or their fragments, able to bind antigens overexpressed in the tumors, have demonstrated potential in PDT of tumors. This review provides an overview of the most recent advances on photoimmunoconjugates (PICs) for cancer PDT, which involve the first and second-generation PSs conjugated to Abs. This is an update of our previous review “Antibodies armed with photosensitizers: from chemical synthesis to photobiological applications”, published in 2015 in Org. Biomol. Chem.
关键词： Photoimmunoconjugates,Antibody conjugation,Photosensitizers,Cancer treatment,Photodynamic therapy
更新于2025-09-23 15:22:29
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A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy
摘要： Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles TB@PMP for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.
关键词： chemotherapy,polymeric prodrug,cancer treatment,photodynamic therapy,nanoparticles
更新于2025-09-23 15:21:21
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Lipid-wrapped Upconversion Nanoconstruct /Photosensitizer Complex for Near-Infrared Light-mediated Photodynamic Therapy
摘要： Photodynamic therapy (PDT) is a non-invasive medical technology that has been applied in cancer treatment where it is accessible by direct or endoscope-assisted light irradiation. To lower phototoxicity and increase tissue penetration depth of light, great effort has been focused on developing new sensitizers that can utilize red or near-infrared (NIR) light for the past decades. Lanthanide-doped upconversion nanoparticles (UCNPs) have a unique property to transduce NIR excitation light to UV-Vis emission efficiently. This property allows some low-cost, low-toxicity, visible light commercially available sensitizers, which originally is not suitable for deep tissue PDT, to be activated by NIR light, and has been reported extensively in the past few year. However, some issues still remain in UCNP-assisted PDT platform such as colloidal stability, photosensitizer loading efficiency, and accessibility for targeting ligand installation, despite some advances in this direction. In this study, we designed a facile phospholipids-coated UCNP method to generate a high-colloidally stable nanoplatform that can effectively load a series of visible light sensitizers in the lipid layers. The loading stability and singlet oxygen generation efficiency of these sensitizers loaded lipid-coated UCNP platform were investigated. We also have demonstrated the enhanced cellular uptake efficiency and tumor cell selectivity of this lipid-coated UCNP platform by changing the lipid dopant. On the basis of the evidence of our results, the lipid-complexed UCNP nanoparticles could serve as an effective photosensitizers carrier for NIR light mediated PDT.
关键词： phospholipids,upconversion,photosensitizers,photodynamic therapy,bioimaging
更新于2025-09-23 15:21:21
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Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging
摘要： The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy.
关键词： photodynamic therapy,doxorubicin,theranostics,chemotherapy,porphyrin
更新于2025-09-23 15:21:21
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Evaluation of photodynamic therapy effect along with colistin on pandrug-resistant <i>Acinetobacter baumannii</i>
摘要： Background and Aims: Pandrug-resistant Acinetobacter baumannii (PDRAB) are including colistin resistant starins (CoRAB) which cause infections potentially untreatable infections. Recently, incidence of these strains are increasing worldwide. Therefore, new approaches, methods and strategies are urgently needed for treatment and eradication of infections due to PDRAB. So the aim of this study was to evaluate the efficacy of photodynamic therapy (PDT) in combination treatment with colistin against PDRAB. Materials and Methods: PDRAB which was isolated from burn patients was used as a test strain. PDT carried out in which toluidine blue O (TBO) and light-emitting diode (LED) were used as photosensitizer and radiation source, respectively. Then, the effect of PDT plus colistin was evaluated on CoRAB and the colony-forming units of each tested groups calculated. Finally, confirmation of antibacterial activity of combination therapy was carried out using scanning electron microscope. Results: PDT declined bacterial count in comparing with control group by 83.7% of killing percentage, in other words, less than one log reduction. While PDT in combination with colistin showed high synergetic effect against A. baumannii in all concentrations of colistin tested by 100% of killing percentage with 9-log reduction. Conclusions: According to our results, PDT alone couldn’t eliminate all of the treated bacterial cells. But when combined with colistin, it killed all of the treated bacterial cells in all tested concentrations. Also PDT decreased the minimal inhibitory concentration of colistin against PDRAB by more than 11 fold.
关键词： colistin,Acinetobacter baumannii,wound infection,toluidine blue O,photodynamic therapy,pandrug resistance
更新于2025-09-23 15:21:21