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Photonuclear production of medical isotopes <sup>62,64</sup> Cu using intense laser-plasma electron source
摘要： 62,64Cu are radioisotopes of medical interest that can be used for positron emission tomography (PET) imaging. Moreover, 64Cu has β? decay characteristics that allow for targeted radiotherapy of cancer. In the present work, a novel approach to experimentally demonstrate the production of 62,64Cu isotopes from photonuclear reactions is proposed in which large-current laser-based electron (e?) beams are generated from the interaction between sub-petawatt laser pulses and near-critical-density plasmas. According to simulations, at a laser intensity of 3.4 × 1021 W/cm2, a dense e? beam with a total charge of 100 nC can be produced, and this in turn produces bremsstrahlung radiation of the order of 1010 photons per laser shot, in the region of the giant dipole resonance. The bremsstrahlung radiation is guided to a natural Cu target, triggering photonuclear reactions to produce the medical isotopes 62,64Cu. An optimal target geometry is employed to maximize the photoneutron yield, and 62,64Cu with appropriate activities of 0.18 GBq and 0.06 GBq are obtained for irradiation times equal to their respective half-lives multiplied by three. The detection of the characteristic energy for the nuclear transitions of 62, 64Cu is also studied. The results of our calculations support the prospect of producing PET isotopes with gigabecquerel-level activity (equivalent to the required patient dose) using upcoming high-intensity laser facilities.
关键词： 62,64Cu,laser-plasma electron source,medical isotopes,Photonuclear production,targeted radiotherapy,PET imaging
更新于2025-09-12 10:27:22
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Thulium Laser‐Assisted Versus Conventional Laparoscopic Partial Nephrectomy for the Small Renal Mass
摘要： Mitochondria-targeting cancer therapies have achieved unprecedented advances attributed to their superior ability for improving drug delivery efficiency and producing an enhanced therapeutic effect. Herein, we report a mitochondria-targeting camptothecin (CPT) polyprodrug system (MCPS) covalently decorated with a high-proportioned CPT content, which can realize drug release specifically responsive to a tumor microenvironment. The nonlinear structure of MCPS can form water-soluble unimolecular micelles with high micellar stability and improved drug accumulation in tumoral cells/tissues. Furthermore, a classical mitochondria-targeting agent, triphenylphosphonium bromide, was tethered in this prodrug system, which causes mitochondrial membrane potential depolarization and mediates the transport of CPT into mitochondria. The disulfide bond in MCPS can be cleaved by an intracellular reductant such as glutathione, leading to enhanced destruction of mitochondria DNA and cell apoptosis induced by a high level of reactive oxygen species. The systematic analyses both in vitro and in vivo indicated the excellent tumor inhibition effect and biosafety of MCPS, which is believed to be an advantageous nanoplatform for subcellular organelle-specific chemotherapy of cancer.
关键词： chemotherapy,reduction-activated,mitochondria-targeted,polyprodrug,cancer therapy
更新于2025-09-11 14:15:04
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<i>De Novo</i> -Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and <i>in Vivo</i>
摘要： As the cleaners of cells, lysosomes play an important role in circulating organic matter within cells, recovering damaged organelles, and removing waste via endocytosis. Because lysosome dysfunction is associated with various diseases—lysosomal storage diseases, inherited diseases, rheumatoid arthritis, and even shock—it is vital to monitor the movement of lysosomes in cells and in vivo. To that purpose, a method of optical imaging, super-resolution imaging technology (e.g., SIM and STORM), can overcome the limitations of traditional optical imaging and afford a range of possibilities for fluorescence imaging. However, the short wavelength excitation and easy photobleaching of super-resolution fluorescence probes somewhat problematize super-resolution imaging. As described herein, we designed a low-toxicity, photostable, near-infrared small molecule fluorescence probe HD-Br for use in the super-resolution imaging of lysosomes. The interaction of lysosomes and mitochondria was dynamically traced while using the probe’s properties to label the lysosomes. Because the probe has the optimal near-infrared excitation and emission wavelengths, liver organoid 3D imaging and Caenorhabditis elegans imaging were also performed. Altogether, our findings indicate valuable approaches and techniques for super-resolution 3D and in vivo imaging.
关键词： lysosome-targeted,3D organoids imaging,C. elegans imaging,structured illumination microscopy,nanoaggregates
更新于2025-09-11 14:15:04
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A photo-controlled hyaluronan-based drug delivery nanosystem for cancer therapy
摘要： In this paper, a novel photo-controlled drug-loaded nanomicelles were self-assembled by the amphiphile of hyaluronan-o-nitrobenzyl-stearyl chain (HA-NB-SC) with doxorubicin (DOX) encapsulated within the hydrophobic core. DOX-loaded HA-NB-SC nanomicelles are ~ 139 nm in diameter. CD44-overexpressed HeLa cells can easily take up HA-NB-SC micelles through recognition of HA moiety. DOX-loaded HA-NB-SC nanomicelles could be disassembled upon UV light (365 nm) and consequently, release DOX at desired pathological sites. Furtherly, nitrosobenzaldehyde derivative, photo-induced products of HA-NB-SC and DOX could inhibit the proliferation of HeLa cells together. This strategy may shed some light on delivery of hydrophobic anti-cancer drugs in a controlled manner.
关键词： targeted delivery,photo-controlled,hyaluronan,nanomicelles
更新于2025-09-10 09:29:36
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A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer
摘要： Multi-stimuli-responsive theranostic nanoplatform integrating functions of both imaging and multimodal therapeutics holds great promise for improving diagnosis and therapeutic efficacy. In this study, we reported a pH, glutathione (GSH) and hyaluronidase (HAase) triple-responsive nanoplatform for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT dual-therapy against HER2-overexpressed breast cancer. The nanoplatform was fabricated by functionalizing gold nanorods (GNRs) with hyaluronic acid (HA) bearing pendant hydrazide and thiol groups via Au-S bonds, and subsequently chemically conjugating 5-aminolevulinic acid (ALA), Cy7.5 and anti-HER2 antibody onto HA moiety for PDT, fluorescence imaging and active targeting, respectively. The resulting versatile nanoplatform GNR-HA-ALA/Cy7.5-HER2 had uniform sizes, favorable dispersibility, as well as pH, GSH and HAase triple-responsive drug release manner. In vitro studies demonstrated that HER2 and CD44 receptor-mediated dual-targeting strategy could significantly enhance the cellular uptake of GNR-HA-ALA/Cy7.5-HER2. Under near-infrared (NIR) irradiation, MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy. Pharmacokinetic and biodistribution studies showed that the nanoplatform possessed a circulation half-life of 1.9 h and could be specifically delivered to tumor tissues with an accumulation ratio of 12.8%. Upon the fluorescence imaging-guided PDT/PTT treatments, the tumors were completely eliminated without obvious side effects. The results suggest that the GNR-HA-ALA/Cy7.5-HER2 hold great potential for breast cancer therapy.
关键词： Triple-responsive drug release,Hyaluronic acid,Gold nanorod,Photodynamic and photothermal dual-therapy,Targeted delivery
更新于2025-09-10 09:29:36
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Designing luminescent ruthenium prodrug for precise cancer therapy and rapid clinical diagnosis
摘要： The effective design of a targeted drug delivery system could improve the therapeutic efficacy of anticancer drugs by reducing their undesirable adsorption and toxic side effects. Here, an RGD-peptide functionalized and bioresponsive ruthenium prodrug (Ru-RGD) was designed for both cancer therapy and clinical diagnosis. This prodrug can be selectively delivered to cervical tumor sites to enhance theranostic efficacy. The benzimidazole-based ligand of the complex is susceptible to acidic conditions so, after reaching the tumor microenvironment, ligand substitution occurs and the therapeutic drug is released. The deep-red emissions produced by both one-photon and two-photon excitation increases the potential of Ru-RGD for use in the deep tissue imaging of 3D tumor spheroids. The specific accumulation of the Ru prodrug in tumor sites allows for precise tumor diagnosis and therapy in vivo. Luminescence staining of 38 clinical patient specimens shows that Ru-RGD exhibits differences in binding capability between cervical cancer and normal tissue, with a sensitivity of 95% and a specificity of 100%. This study thus provides an approach for the effective design and application of targeted metal complexes in cancer therapy and clinical diagnosis.
关键词： targeted drug delivery,cancer theranosis,rapid clinical diagnosis,two-photon imaging,tumor microenvironment
更新于2025-09-10 09:29:36
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Integration of PSMA-targeted PET imaging into the armamentarium for detecting clinically significant prostate cancer
摘要： To explore the current state of using prostate-specific membrane antigen (PSMA)-targeted PET imaging to aid in the diagnosis of clinically significant prostate cancer. Prostate-specific antigen screening remains controversial, as it is associated with the underdetection of clinically significant prostate cancer as well as the overdetection and subsequent overtreatment of clinically insignificant disease. A diagnostic test that can accurately assess the presence of clinically significant prostate cancer and avoid detection of low-risk tumors is needed. Multiparametric magnetic resonance imaging (mpMRI) can aid in the detection of clinically significant prostate cancer and can be used with fusion-based biopsy platforms to target biopsies to specific lesions. However, there are several limitations of mpMRI including a modest negative predictive value for high-grade cancer. PSMA-targeted PET imaging has shown promise as a noninvasive test to aid in the detection of clinically significant prostate cancer while providing anatomical information to guide targeted biopsies. PSMA-targeted PET in combination with mpMRI offers a higher degree of diagnostic accuracy for imaging localized prostate cancer than either modality alone. PSMA-targeted PET imaging can aid in the identification of men with clinically significant prostate cancer. Further research is needed to determine the full potential of PSMA-targeted imaging in both the detection and treatment of localized prostate cancer.
关键词： focal therapy,MRI/ultrasound fusion,prostate-specific membrane antigen,prostate cancer,targeted biopsy
更新于2025-09-10 09:29:36
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[ASME ASME 2018 Conference on Smart Materials, Adaptive Structures and Intelligent Systems - San Antonio, Texas, USA (Monday 10 September 2018)] Volume 1: Development and Characterization of Multifunctional Materials; Modeling, Simulation, and Control of Adaptive Systems; Integrated System Design and Implementation - Essentially Nonlinear Piezoelectric Attachment for Aeroelastic Flutter Suppression
摘要： Various researchers have investigated the behavior of a linear mechanical oscillator weakly coupled to a nonlinear mechanical attachment that has essential stiffness nonlinearity. Under certain conditions, the essentially nonlinear attachment acts as a nonlinear energy sink (NES) and one-way energy transfer from the main structure to the attachment can be achieved. Since an essentially nonlinear attachment does not possess any preferential resonance frequency, they have increased robustness against detuning, enabling frequency-wise wideband performance. In this work, the interactions between an essentially nonlinear piezoelectric an electromechanically coupled two-degree-of-freedom (2-DOF) aeroelastic typical section are studied. The governing equations of typical section with piezoelectric coupling added to the plunge DOF are presented. An equivalent electrical model of the coupled aeroelastic system is presented and combined to a nonlinear shunt circuit. The performance of the piezoelectric NES to modify the aeroelastic behavior of the typical section is discussed using the short-circuit condition as a reference case. Furthermore, the robustness of the piezoelectric NES against detuning is also investigated by changing some parameters of the typical section.
关键词： piezoelectric,aeroelastic,flutter suppression,nonlinear energy sink,targeted energy transfer
更新于2025-09-09 09:28:46
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[Methods in Molecular Biology] Atomic Force Microscopy Volume 1886 (Methods and Protocols) || Molecular Recognition Force Spectroscopy for Probing Cell Targeted Nanoparticles In Vitro
摘要： In the development and design of cell targeted nanoparticle-based systems the density of targeting moieties plays a fundamental role in allowing maximal cell-specific interaction. Here, we describe the use of molecular recognition force spectroscopy as a valuable tool for the characterization and optimization of targeted nanoparticles toward attaining cell-specific interaction. By tailoring the density of targeting moieties at the nanoparticle surface, one can correlate the unbinding event probability between nanoparticles tethered to an atomic force microscopy tip and cells to the nanoparticle vectoring capacity. This novel approach allows for a rapid and cost-effective design of targeted nanomedicines reducing the need for long and tedious in vitro tests.
关键词： Targeted nanoparticles,Tailored nanomedicine,Tip functionalization,Single molecule force spectroscopy,Drug delivery
更新于2025-09-09 09:28:46
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Stable Mesoporous Silica Nanoparticles Incorporated with MoS2 and AIE for Targeted Fluorescence Imaging and Photothermal Therapy of Cancer Cells
摘要： Theranostics for imaging-guided cancer treatment have obtained great attention in recent years for their outstanding capability of both tumor diagnosis and treatment. Molybdenum disulfide (MoS2) nanosheets revealed excellent photothermal conversion efficiency, which could be used as photothermal agents. However, MoS2 nanosheets would often quench or decrease the emission of fluorescence dyes when they were incorporated with these dyes to construct fluorescence-imaging-guided nanotheranostic systems. In this work, MoS2 nanosheets were embedded into mesoporous silica nanoparticles (MSNs), and Aggregation Induced Emission (AIE) fluorogen PhENH2 was chemically modified on the surface of MSNs, which could demonstrate more stable fluorescence emission compared with other MSNs with physically absorbed luminescent molecules. Moreover, folic acid (FA) was also chemically decorated on the nanoparticles to facilitate their targeted bioimaging and photothermal therapy. As expected, the obtained PhENH2-MoS2-FA MSNs could be efficiently taken up by MDA-MB-231 cells than HepG2 cells, owing to the over-expressed FA receptors on MDA-MB-231 cells. Meanwhile, these MDA-MB-231 cells could be efficiently killed under an 808 nm laser irradiation. These results indicated that the achieved multifunctional MSNs chemically decorated with AIE fluorogens would demonstrate more stable fluorescence for bioimaging-targeted photothermal therapy of MDA-MB-231 cells, which made them promising nanotheranostics for further cancer treatment.
关键词： Photothermal Therapy,Molybdenum Disulfide,Targeted Fluorescence Imaging,Aggregation Induction Emission,Stability
更新于2025-09-09 09:28:46