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Near-Infrared Light Triggered Sulfur Dioxide Gas Therapy of Cancer
摘要： The exploitation of gas therapy platforms holds great promise as a 'green' approach for selective cancer therapy, however, it is often associated with some challenges, such as uncontrolled or insufficient gas generation and unclear therapeutic mechanisms. In this work, a gas therapy approach based on near-infrared (NIR) light triggered sulfur dioxide (SO2) generation was developed, and the therapeutic mechanism as well as in vivo anti-tumor therapeutic efficacy was demonstrated. A SO2 prodrug-loaded rattle-structured upconversion@silica nanoparticles (RUCSNs) was constructed to enable high loading capacity without obvious leakage, and to convert NIR light into ultraviolet (UV) light so as to activate the prodrug for SO2 generation. In addition, SO2 prodrug-loaded RUCSNs showed high cell uptake, good biocompatibility, intracellular tracking ability, and high NIR light triggered cytotoxicity. Furthermore, the cytotoxic SO2 was found to induce cell apoptosis accompanied with the increase of intracellular reactive oxygen species (ROS) levels and the damage of nuclear DNA. Moreover, efficient inhibition of tumor growth was achieved, associated with significantly prolonged survival of mice. Such NIR light-triggered SO2 therapy may provide an effective strategy to stimulate further development of synergistic cancer therapy platforms.
关键词： upconversion nanoparticles (UCNPs),gas therapy,cancer therapy,near-infrared (NIR),sulfur dioxide (SO2)
更新于2025-09-23 15:22:29
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CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy
摘要： Combined photothermal and gene therapy provides a promising modality toward cancer treatment, yet facile integration and controlled codelivery of gene payloads and photothermal conversion agents (PTCAs) remains a great challenge. Inspired by the robust wet adhesion of marine mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%). Moreover, a successful calcium phosphate (CaP) coating via biomineralization was constructed on the cationic nanoparticle to prohibit premature release of siRNA. The CaP coating underwent biodegradation in weakly-acidic subcellular conditions (lysosomes). The synergistic integration of tertiary amines and catechol moieties on the subsequently exposed surfaces was demonstrated to feature the destabilization/disruption ability toward model cellular membranes via the greatly enhanced interfacial adhesion and interactions. Consequently, sufficient permeability of lysosomal membranes, and in turn, a high lysosomal escape efficiency, was realized, which then resulted in high gene silencing efficiencies via sufficient cytosolic delivery of siRNA. When an efficient knocking down (65%) of survivin (an inhibitor of apoptosis proteins) was combined with a subsequent photothermal ablation, remarkably higher therapeutic efficiencies were observed both in vitro and in vivo, as compared with monotherapy. The system may help to pave a new avenue on the utilization of bio-adhesive surfaces for handling the obstacles of combined photothermal and gene therapy.
关键词： porous polydopamine nanocarriers,bioadhesion,lysosomal escape,siRNA delivery,photothermal therapy
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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A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy
摘要： The current interest in cancer research is being shifted from individual therapy to combinatorial therapy. In this contribution, a novel multifunctional nanoplatform comprising alginate nanogel co-loaded with cisplatin and gold nanoparticles (AuNPs) has been firstly developed to combine photothermal therapy and chemotherapy. The antitumor efficacy of the as-prepared nanocomplex was tested against CT26 colorectal tumor model. The nanocomplex showed an improved chemotherapy efficacy than free cisplatin and caused a significantly higher tumor inhibition rate. The in vivo thermometry results indicated that the tumors treated with the nanocomplex had faster temperature rise rate under 532 nm laser irradiation and received dramatically higher thermal doses due to optical absorption properties of AuNPs. The combined action of chemo-photothermal therapy using the nanocomplex dramatically suppressed tumor growth up to 95% of control and markedly prolonged the animal survival rate. Moreover, tumor metabolism was quantified by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging and revealed that the combination of the nanocomplex and laser irradiation have the potential to eradicate microscopic residual tumor to prevent cancer relapse. Therefore, the nanocomplex can afford a potent anticancer efficacy whereby heat and drug can be effectively deliver to the tumor, and at the same time the high dose-associated side effects due to the separate application of chemotherapy and thermal therapy could be potentially reduced.
关键词： Alginate,Cisplatin,Gold nanoparticles,Chemo-photothermal therapy,Positron emission tomography
更新于2025-09-23 15:22:29
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Conformal image-guided microbeam radiation therapy at the ESRF biomedical beamline ID17
摘要： Purpose: Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target. Methods: This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles. Results: Using four external fiducial markers of 1.7 mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2 mm can be achieved with an angular deviation of less than 2?. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1 mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam. Conclusions: The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials.
关键词： microbeam radiation therapy,image-guidance,x-ray imaging,fiducial markers,synchrotron radiation
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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Dark-Adaptation Functions in Molecularly Confirmed Achromatopsia and the Implications for Assessment in Retinal Therapy Trials
摘要： PURPOSE. To describe the dark-adaptation (DA) functions in subjects with molecularly proven achromatopsia (ACHM) using refined testing conditions with a view to guiding assessment in forthcoming gene therapy trials. METHODS. The DA functions of nine subjects with ACHM were measured and compared with those of normal observers. The size and retinal location of the stimuli used to measure DA sensitivities were varied in four distinct testing condition sets, and the effect of altering these parameters assessed. RESULTS. In three of the four testing condition sets, achromats had significantly higher mean final thresholds than normal observers, whereas in the fourth condition set they did not. A larger, more central stimulus revealed the greatest difference between the final DA thresholds of achromat and normal subjects, and also demonstrated the slowest rate of recovery among the achromat group. CONCLUSIONS. In this, the largest study of DA functions in molecularly proven ACHM to date, we have identified optimal testing conditions that accentuate the relative difference between achromats and normal observers. These findings can help optimize DA testing in future trials, as well as help resolve the dichotomy in the literature regarding the normality or otherwise of DA functions in ACHM. Furthermore, the shorter testing time and less intense adaptation light used in these experiments may prove advantageous for more readily and reliably probing scotopic function in retinal disease, and be particularly valuable in the frequent post therapeutic assessments required in the context of the marked photophobia in ACHM.
关键词： rod monochromatism,dark adaptation,achromatopsia,rod vision,gene therapy
更新于2025-09-23 15:22:29
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Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]
摘要： Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. Acronym: PSMA-SRT Phase 3 trial.
关键词： Randomized phase 3 trial,PET/CT,Prostate cancer,PSMA,Salvage radiation therapy
更新于2025-09-23 15:22:29