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Sensitive, Real-Time and In-Vivo Oxygen Monitoring for Photodynamic Therapy by Multifunctional Mesoporous Nanosensors
摘要： Real-time monitoring of oxygen consumption is beneficial to predict treatment response and optimize therapeutic protocols for photodynamic therapy (PDT). In this work, we first demonstrate that deformable hollow mesoporous organosilica nanoparticles (HMONs) can be used to load [(Ru(dpp)3)]Cl2 for detecting oxygen (denoted as HMON-[(Ru(dpp)3)]Cl2). This nanoprobe shows significantly improved biocompatibility and high cellular uptake. In-vitro eperiments demonstrate that the HMON-[(Ru(dpp)3)]Cl2 can sensitively detect oxygen changes between 1 %-20 %. On this basis, photosensitizer chlorin e6 (Ce6) and [(Ru(dpp)3)]Cl2 are simultaneously loaded in the HOMNs (denoted as HMON-Ce6-[(Ru(dpp)3)]Cl2) for real-time oxygen monitoring during photodynamic therapy. The HMON-Ce6-[(Ru(dpp)3)]Cl2 can reflects oxygen consumption in solution and cells in photodynamic therapy. Furthermore, the ability of HMON-Ce6-[(Ru(dpp)3)]Cl2 nanosensor to monitor oxygen changes is demonstrated in tumor-bearing nude mice.
关键词： oxygen detection,mesoporous organosilica,photodynamic therapy,in-vivo,real-time
更新于2025-09-04 15:30:14
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Folic acid-nanoscale gadolinium-porphyrin metal-organic frameworks: fluorescence and magnetic resonance dual-modality imaging and photodynamic therapy in hepatocellular carcinoma
摘要： Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and severely threatens human health. Since the prognosis of advanced HCC remains poor, there is an urgent need to develop new therapeutic approaches. Porphyrin metal-organic frameworks are a class of porous organic-inorganic hybrid functional materials with good biocompatibility. Methods: Gadolinium-porphyrin metal-organic frameworks were used as a skeleton for folic acid (FA) conjugation to synthesize a novel type of nanoparticle, denoted as folic acid-nanoscale gadolinium-porphyrin metal-organic frameworks (FA-NPMOFs). The FA-NPMOFs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric-differential thermal analysis. The biotoxicity and imaging capability of the FA-NPMOFs were determined using HepG2 cells and embryonic and larval zebrafish. The delivery and photodynamic therapeutic effect of FA-NPMOFs were explored in transgenic zebrafish with doxycycline-induced HCC. Results: FA-NPMOFs were spherical in structure with good dispersion and water solubility. They showed low biotoxicity, emitted bright red fluorescence, and exhibited an excellent magnetic resonance imaging capability, both in vitro and in vivo. Meanwhile, the FA-NPMOFs exhibited a strong affinity for folate receptor (FR)-expressing cells and were delivered to the tumor site in a targeted manner. Moreover, HCC tumor cells were eliminated following laser irradiation. Conclusion: FA-NPMOFs can be used for dual-modality imaging and photodynamic therapy in HCC and show promise for use as a carrier in new therapies for HCC and other FR-positive tumors.
关键词： nanoscale gadolinium-porphyrin metal-organic frameworks,folic acid,hepatocellular carcinoma,photodynamic therapy,dual-modality imaging
更新于2025-09-04 15:30:14
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Radiation-responsive scintillating nanotheranostics for reduced hypoxic radioresistance under ROS/NO-mediated tumor microenvironment regulation
摘要： Abstract: Hypoxia-induced radioresistance is the primary reason for failure of tumor radiotherapy (RT). Changes within the irradiated tumor microenvironment (TME) including oxygen, reactive oxygen species (ROS) and nitric oxide (NO) are closely related to radioresistance. Therefore, there is an urgent need to develop new approaches for overcoming hypoxic radioresistance by incorporating TME regulation into current radiotherapeutic strategies. Methods: Herein, we explored a radiation-responsive nanotheranostic system to enhance RT effects on hypoxic tumors by multi-way therapeutic effects. This system was developed by loading S-nitrosothiol groups (SNO, a NO donor) and indocyanine green (ICG, a photosensitizer) onto mesoporous silica shells of Eu3+-doped NaGdF4 scintillating nanocrystals (NSC). Results: Under X-ray radiation, this system can increase the local dosage by high-Z elements, promote ROS generation by X-ray-induced photodynamic therapy, and produce high levels of NO to enhance tumor-killing effects and improve hypoxia via NO-induced vasodilation. In vitro and in vivo studies revealed that this combined strategy can greatly reinforce DNA damage and apoptosis of hypoxic tumor cells, while significantly suppressing tumor growth, improving tumor hypoxia and promoting p53 up-regulation and HIF1α down-regulation. In addition, this system showed pronounced tumor contrast performance in T1-weighted magnetic resonance imaging and computed tomography. Conclusion: This work demonstrates the great potential of scintillating nanotheranostics for multimodal imaging-guided X-ray radiation-triggered tumor combined therapy to overcome radioresistance.
关键词： X-ray induced photodynamic therapy,hypoxia-induced radioresistance,nanoscintillators,multimodal imaging,nitric oxide
更新于2025-09-04 15:30:14
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A two-year study of diffused retinal pigment epitheliopathy treated with half-dose photodynamic therapy guided by simultaneous angiography and optical coherence tomography
摘要： Objectives Diffused retinal pigment epitheliopathy (DRPE) is not necessarily the same as chronic central serous chorioretinopathy (CSC), but a severe subgroup under the umbrella of chronic CSC. This study was to evaluate the efficacy and safety of half-dose PDT treating DRPE. Methods A retrospective case series design was used. Forty-eight consecutive patients (48 eyes) with DRPE treated with half-dose PDT underwent follow-up at baseline, 3 months, 6 months, 12 months and 24 months. Simultaneous FA, ICGA and OCT were used for the treatment and follow-up. The primary outcomes were the subretinal fluid and best-corrected visual acuity in optical coherence tomography. Results Complete fluid absorption was achieved in 95.8% of eyes at 3 months and 100.0% of eyes at 24 months. The baseline logarithm of the minimum angle of resolution (logMAR) BCVA, which was 0.51 ± 0.36, significantly improved to 0.43 ± 0.38 (p < 0.001) at 6 months. The boost continued to 0.29 ± 0.37 (p < 0.001) at 12 months and 0.19 ± 0.39 (p < 0.001) at 24 months. The integrities of the ellipsoid zone (EZ) and interdigitation zone (IZ) improved throughout. Regression analyses showed the BCVA in logMAR was inversely correlated with the EZ (p < 0.01) and IZ (p < 0.01). The recurrence rate was 6.3%. No severe complications were witnessed. Conclusions In 48 eyes with DRPE, simultaneous angiography and OCT facilitated a more comprehensive guidance for half-dose PDT treatment and follow-up. The BCVA improvement occurred at 6 months, which may be attributed to the restoration of the outer retinal structure.
关键词： chronic central serous chorioretinopathy,half-dose photodynamic therapy,Diffused retinal pigment epitheliopathy,angiography,CSC,optical coherence tomography,OCT,DRPE,PDT
更新于2025-09-04 15:30:14
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In Vitro antimicrobial photoinactivation with methylene blue in different microorganisms
摘要： Aim: To evaluate the in vitro antimicrobial effects of photodynamic therapy (PDT). Methods: The microorganism indicators were: Candida albicans, Pseudomonas aeruginosa,Enterococcus faecalis and Staphylococcus aureus. A microbial pool was prepared (108 cells/mL), from which aliquots were transferred to culture plates for carrying out the PDT using methylene blue (50 μM) and low-power laser (660 nm, 100 mW and 9 J).The effect of methylene blue alone, low power laser and the absence of treatments were evaluated. Then, aliquots of 1 μL were plated in a media culture, the number of colony forming units (CFU/mL) was obtained and the data submitted to the F test (ANOVA) with Tamhane’s comparisons. Results:The laser radiation in the presence of methylene blue was able to eliminate 74.90% of C. albicans, 72.41% of P. aeruginosa, 96.44% of E. faecalis and 95.42% of S. aureus, thus statistically significant differences were found among the groups (p<0.001). Conclusions: PDT was effective in reducing the number of viable cells in the studiedmicroorganisms, especially E. faecalis and S. aureus.
关键词： microbiology,Enterococcus faecalis,methylene blue,endodontics,photodynamic therapy
更新于2025-09-04 15:30:14
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Nano-Assemblies from J-Aggregated Dyes: A Stimuli-Responsive Tool Applicable to Living Systems
摘要： Controlling the packing arrangements of dyes is a facile way of tuning their photophysical and/or photochemical properties, thus enabling new sensing mechanisms for photofunctional tools. Here, we present a general and robust strategy toward water-stable J-aggregated dye templated nano-assemblies by incorporating an amphiphilic diblock copolymer and a stimuli-responsive dye as the only two building components. An iodo-substituted boron dipyrromethene (BODIPY) was adopted as a template to direct the self-assembly of poly(ethylene glycol)-block-polycaprolactone (PEG-PCL), forming a core-shell nanoplate with slip-stacked BODIPYs as core surrounded by hydrophilic PEG shell. The self-assembled nanoplate is stable in cell culture medium and possesses a built-in stimuli-responsiveness that arises from BODIPY bearing meso-carboxylate protecting group, which is efficiently removed upon treatment with peroxynitrite. The resulting negative charges lead to rearrangement of dyes from J-stacking to non-stacking, which activates photoinduced singlet oxygen production from the nano-assemblies. The stimuli-activatable photosensitivity has been exploited for specific photodynamic ablation of activated RAW 264.7 cells with excessive endogenous peroxynitrite. In light of the generality of the sensing mechanism, the concept described herein will significantly expands the palette of design principles to develop diverse photofunctional tools for biological research and clinical needs.
关键词： J-aggregated dyes,PEG-PCL,photodynamic therapy,nano-assemblies,BODIPY,stimuli-responsive
更新于2025-09-04 15:30:14