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Selectivity in Photodynamic Action: Higher Activity of Mitochondria Targeting Photosensitizers in Cancer Cells
摘要： Among the pathways for improving the practice of photodynamic therapy of cancer, increasing the selectivity of photodynamic action is an obvious choice. Considering the different characteristics of mitochondria in normal cells and cancer cells, we designed mitochondria targeting photosensitizers. We now demonstrate that mitochondria targeted photosensitizers by TPP-derivatization, are more selective for cancer cells compared to normal cells, presumably due to larger membrane potential of cancer cell mitochondria allowing more efficient accumulation of the photosensitizer.
关键词： organelle targeting,photodynamic action,singlet oxygen,photosensitizers,photodynamic therapy
更新于2025-09-23 15:22:29
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A self-illuminating nanoparticle for inflammation imaging and cancer therapy
摘要： Nanoparticles have been extensively used for inflammation imaging and photodynamic therapy of cancer. However, the major translational barriers to most nanoparticle-based imaging and therapy applications are the limited depth of tissue penetration, inevitable requirement of external irradiation, and poor biocompatibility of the nanoparticles. To overcome these critical limitations, we synthesized a sensitive, specific, biodegradable luminescent nanoparticle that is self-assembled from an amphiphilic polymeric conjugate with a luminescent donor (luminol) and a fluorescent acceptor [chlorin e6 (Ce6)] for in vivo luminescence imaging and photodynamic therapy in deep tissues. Mechanistically, reactive oxygen species (ROS) and myeloperoxidase generated in inflammatory sites or the tumor microenvironment trigger bioluminescence resonance energy transfer and the production of singlet oxygen (1O2) from the nanoparticle, enabling in vivo imaging and cancer therapy, respectively. This self-illuminating nanoparticle shows an excellent in vivo imaging capability with suitable tissue penetration and resolution in diverse animal models of inflammation. It is also proven to be a selective, potent, and safe antitumor nanomedicine that specifically kills cancer cells via in situ 1O2 produced in the tumor microenvironment, which contains a high level of ROS.
关键词： photodynamic therapy,cancer therapy,inflammation imaging,reactive oxygen species,myeloperoxidase,bioluminescence resonance energy transfer,nanoparticles
更新于2025-09-23 15:22:29
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A molecular hybrid producing simultaneously singlet oxygen and nitric oxide by single photon excitation with green light
摘要： Combination of photosensitizers (PS) for photodynamic therapy with NO photodonors (NOPD) is opening intriguing horizons towards new and still underexplored multimodal anticancer and antibacterial treatments not based on “conventional” drugs and entirely controlled by light stimuli. In this contribution, we report an intriguing molecular hybrid based on a BODIPY light-harvesting antenna that acts simultaneously as PS and NOPD upon single photon excitation with the highly biocompatible green light. The presented hybrid offers a combination of superior advantages with respect to the other rare cases reported to date, meeting most of the key criteria for both PSs and NOPDs in the same molecular entity such as: (i) capability to generate 1O2 and NO with single photon excitation of biocompatible visible light, (ii) excellent 1O2 quantum yield and NO quantum efficiency, (iii) photogeneration of NO independent from the presence of oxygen, (iv) large light harvesting properties in the green region. Furthermore, this compound together with its stable photoproduct, is well tolerated by both normal and cancer cells in the dark and exhibits bimodal photomortality of cancer cells under green light excitation due to the combined action of the cytotoxic 1O2 and NO.
关键词： Green light,Nitric oxide,Multimodal therapy,Singlet oxygen,BODIPY,Photodynamic therapy
更新于2025-09-23 15:22:29
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Biodegradable Micelles for NIR/GSH-Triggered Chemophototherapy of Cancer
摘要： The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.
关键词： photothermal therapy,photodynamic therapy,biodegradable,stimuli-responsive drug delivery systems,cypate
更新于2025-09-23 15:22:29
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Carbon Nanomaterials for Bioimaging, Bioanalysis, and Therapy || Photoacoustic Imaging with Carbon Nanomaterials
摘要： Photoacoustic imaging is a novel, noninvasive biomedical imaging modality that has evolved considerably over the last few decades. As a label‐free imaging modality using both endogenous and exogenous contrast agent it has shown many advantages to safely and effectively differentiate diseased tissue from healthy tissues at a deeper depth. While endogenous light‐absorbing objects in living subjects such as hemoglobin, melanin, and glucose, have been useful in imaging, the use of exogenous contrast agents can improve the detection sensitivity and specific tissue‐targeting capabilities of photoacoustic imaging modality further. The carbon nanomaterial has been found to be one of the best contrast agents for photoacoustic imaging, which has strong absorption properties and great biocompatibility. This chapter covers the basic introduction of photoacoustic imaging and the application of carbon nanomaterials contrast agent such as imaging‐guided therapy and multimodal imaging in photoacoustic imaging.
关键词： photoacoustic imaging,contrast agents,photothermal therapy,photodynamic therapy,multimodal imaging,biomedical imaging,carbon nanomaterials
更新于2025-09-23 15:22:29
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Light-responsive nanoparticles based on new polycarbonate polymers as innovative drug delivery systems for photosensitizers in PDT
摘要： Nanoparticles based on biodegradable polymers are well-known as approved carrier systems for a diversity of drugs. Despite their advantages, such as the option of an active drug targeting or the physicochemical protection of instable payloads, the controlled drug release often underlies intra- and interindividual influences and is therefore difficult to predict. To circumvent this limitation, the release behavior can be optimized using light-responsive materials for the nanoparticle preparation. The resulting light-responsive nanoparticles are able to release the embedded drug after an external light-stimulus, thereby increasing efficacy and safety of the therapy. In the present study light-responsive self-immolative polymers were used for the nanoparticle manufacturing. Light-responsive polycarbonates (LrPC) as well as PEGylated LrPC (LrPC-PEG) were synthesized via ring-opening polymerization of trimethylene carbonate-based monomers and fully physico-chemically characterized. Light-responsive nano formulations were obtained by blending LrPC or (LrPC-PEG) with the FDA-approved polymer poly(lactic-co-glycolic-acid) (PLGA). The nanoparticles were loaded with the photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). The light-induced nanoparticle degradation was analyzed as well as the drug release behavior with and without illumination. Furthermore, biological safety of the degradation products was investigated in an in vitro cell culture study.
关键词： light-responsive polymers,Nanoparticles,intestinal cancer,photodynamic therapy,poly(lactic-co-glycolic acid)
更新于2025-09-23 15:22:29
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Preparation of a star-shaped copolymer with porphyrin core and four PNIPAM-b-POEGMA arms for photodynamic therapy
摘要： A series of thermosensitive star-shaped copolymers THPP-(PNIPAM-b-POEGMA)4 with 5, 10, 15,20-tetrakis-(4-hydroxyphenyl)-21H,23H-porphyrin (THPP) core and four poly(N-isopropylacrylamide)-b-poly(oligo(ethylene glycol) mono methyl ether methacrylate) (PNIPAM-b-POEGMA) arms were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The low critical solution temperatures (LCSTs) of THPP-(PNIPAM-b-POEGMA)4 with different molecular weights were 37.5 °C, 39.9 °C and 41.9 °C respectively, which depending on the hydrophilic POEGMA contents of copolymers. The micellar structures of copolymers could be formed above the LCSTs. The MTT study indicated that THPP-(PNIPAM-b-POEGMA)4 and THPP showed no significant cytotoxicity toward HeLa cells and L929 cells. And THPP-(PNIPAM-b-POEGMA)4 under light irradiation showed photodynamic activity which photo-toxicity toward HeLa cells was stronger than THPP.
关键词： Porphyrin,Thermosensitivity,Reversible addition-fragmentation chain transfer (RAFT),THPP-(PNIPAM-b-POEGMA)4,Photodynamic therapy
更新于2025-09-23 15:22:29
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Antimicrobial photodynamic therapy with phenothiazinium photosensitizers in non-vertebrate model Galleria mellonella infected with Fusarium keratoplasticum and Fusarium moniliforme
摘要： Fusarium keratoplasticum and Fusarium moniliforme are filamentous fungi common in the environment and cause mycosis in both animals and plants. Human infections include mycetoma, keratitis and onychomycosis, while deeper mycosis occurs in immunocompromised patients. Most of the Fusarium spp. are frequently resistant to treatment with currently used antifungals. The frequent occurrence of antifungal resistance has motivated the study of antimicrobial photodynamic therapy as an alternative treatment for fungal infections. Many studies have investigated the in vitro use of antimicrobial photodynamic therapy to kill fungi, but rarely in animal models of infection. Thus, here we employed the invertebrate wax moth Galleria mellonella to study the in vivo effects of antimicrobial photodynamic therapy with three different phenothiazinium photosensitizers, methylene blue, new methylene blue N and the pentacyclic S137 against infection with microconidia of Fusarium keratoplasticum and Fusarium moniliforme. The effect of antimicrobial photodynamic therapy using these photosensitizers and light-emitting diodes with an emission peak at 635 nm and an integrated irradiance from 570 to 670 nm of 9.8 mW cm?2 was investigated regarding the toxicity, fungal burden, larval survival and cellular immune response. The results from this model indicate that antimicrobial photodynamic therapy with methylene blue, new methylene blue N and S137 is efficient for the treatment of infection with F. keratoplasticum and F. moniliforme. The efficiency can be attributed to the fungal cell damage caused by antimicrobial photodynamic therapy which facilitates the action of the host immune response.
关键词： Antimicrobial photodynamic therapy,Fusarium keratoplasticum,Galleria mellonella,Mycosis,Fusarium moniliforme
更新于2025-09-23 15:22:29
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Photodynamic Therapy at Low-Light Fluence Rate: in vitro Assays on Colon Cancer Cells
摘要： This paper presents the results of in vitro photodynamic therapy assays on RKO and HCT-15 cell lines. The envisaged implementation is in autonomous medical microdevices, such as endoscopic capsules for clinical treatment of several types of gastrointestinal tract tumors. Because of their very limited device volume, light fluence and fluence rate needed to destroy tumor cells should be minimized. Foscan or meta-tetra(hydroxyphenyl)chlorin (mTHPC) is used as a photosensitizer. The experimental results show that a small amount of mTHPC (0.15 mg/kg) and light fluence (5–20 J/cm2) is sufficient to obtain significant photodynamic activity. An array of LEDs with peak transmittance at 652 nm is used as a portable light source for the maximum quantum efficiency in producing singlet oxygen. Irradiation to a light fluence between 2.5 and 10 J/cm2 is achieved by an increased exposure time at an 11 mW/cm2 light fluence rate, while mTHPC concentrations of 0.5, 1, 5, and 10 μg/mL are used. The experimental results show that decreased cell viability (down to 30%) can be obtained for 1–5 μg/mL of mTHPC concentrations and 2.5 J/cm2 of light fluence. Such light fluence and light fluence rate are compatible with the endoscopic capsules batteries.
关键词： Biophotonic therapeutic technique,Photodynamic therapy,light-tissue interaction
更新于2025-09-23 15:22:29
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Photodynamic Therapy With Bengal Rose and Derivatives Against Leishmania amazonensis
摘要： Introduction: The treatment of cutaneous leishmaniasis (CL) is based primarily on the use of pentavalent antimonials, which may lead to many side effects limiting their use. Photodynamic therapy (PDT) is an alternative for the treatment of CL, and some xanthene dyes have the potential for use in PDT. Methods: The xanthenes rose bengal B (RB) and its derivatives rose bengal methyl ester (RBMET), and butyl ester (RBBUT) were analyzed for leishmanicidal activity against promastigotes and intracellular amastigotes of Leishmania amazonensis. Cytotoxicity was assessed in J774.A1 macrophages. Results: RB derivates RBMET (IC50 9.83 μM), and RBBUT (IC50 45.08 μM) showed leishmanicidal activity, however, were toxic to J774.A1 macrophages, resulting in low selectivity index. Conclusion: The RBMET and RBBUT showed to be effective against the L. amazonensis and the low selectivity index presented may not be a limitation for their use in PDT to CL treatment.
关键词： Photodynamic therapy,Xanthenes,Rose Bengal B,Leishmania amazonensis,Cutaneous leishmaniasis
更新于2025-09-23 15:22:29