Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm(-2)). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy.
Lanthanide-based multimodal probes with high sensitivity, simple synthesis strategy, and good biocompatibility promise new applications for clinical diagnosis. However, today's challenge is not only to develop high-performance multimodal probes for more accurate and reliable diagnosis, but also to understand the fate of these probes in vivo. In this context, a novel PEGylated Dy-doped NaGdF4 nanoprobe (PEG-NaGdF4:Dy) was designed and fabricated as a T1/T2-weighted MRI/CT imaging agent. This nanoprobe has a distinct longitudinal relaxivity (r1 = 5.17 mM(-1) s(-1)), relatively high transverse relaxivity (r2 = 10.64 mM(-1) s(-1)), and exhibits strong X-ray attenuation properties (44.70 HU L g(-1)) in vitro. Furthermore, T1/T2-weighted MRI/CT imaging in vivo confirmed that this PEG-NaGdF4:Dy nanoprobe could lead to a significant contrast enhancement effect on liver, spleen and kidney at 24 h post injection. The MTT assay, histological analysis, and biodistribution investigation demonstrated that this multifunctional nanoprobe possessed relatively low cytotoxicity, negligible tissue damage and could be completely excreted out of the body of mice as time prolonged. Therefore, the present PEG-NaGdF4:Dy nanoprobe has the potential for the development of multifunctional T1/T2-weighted MRI/CT imaging to provide more comprehensive and accurate diagnosis information.
Silver-containing antimicrobial agents are used in various medical products. However, their toxicity to mammalian cells has not been sufficiently evaluated. Numerous studies have unveiled evidence of significant antimicrobial properties associated with Ag ions. In cell culture media or human body fluids, the free Ag(+) has rich opportunities to complex with Cl(-). Surprisingly, studies on the toxicity of solid form AgCl(s) to mammalian cells are quite limited. In this study, we evaluated the cytotoxicity of Ag ions and silver chloride colloids on red blood cells and human mesenchymal stem cells (hMSCs). The adverse effects of silver chloride on red blood cells and hMSC were viewed by SEM and LIVE/DEAD viability staining, respectively. Among different tested chemical forms of silver, AgCl was identified to be the least cytotoxic. Moreover, a decline in the cytotoxicity of AgCl at significantly high concentrations was observed. We attributed the reduced cytotoxicity to aggregated AgCl which limited the bioavailability of free Ag(+) ions.
Nanomaterials have gained considerable attention and interest in the development of novel and high-resolution contrast agents for medical diagnosis and prognosis in clinic. A classical urea-based homogeneous precipitation route that combines the merits of in situ thermal decomposition and surface modification is introduced to construct polyethylene glycol molecule (PEG)-decorated hybrid lutetium oxide nanoparticles (PEG-UCNPs). By utilizing the admirable optical and magnetic properties of the yielded PEG-UCNPs, in vivo up-conversion luminescence and T1 -enhanced magnetic resonance imaging of small animals are conducted, revealing obvious signals after subcutaneous and intravenous injection, respectively. Due to the strong X-ray absorption and high atomic number of lanthanide elements, X-ray computed-tomography imaging based on PEG-UCNPs is then designed and carried out, achieving excellent imaging outcome in animal experiments. This is the first example of the usage of hybrid lutetium oxide nanoparticles as effective nanoprobes. Furthermore, biodistribution, clearance route, as well as long-term toxicity are investigated in detail after intravenous injection in a murine model, indicating the overall safety of PEG-UCNPs. Compared with previous lanthanide fluorides, our nanoprobes exhibit more advantages, such as facile construction process and nearly total excretion from the animal body within a month. Taken together, these results promise the use of PEG-UCNPs as a safe and efficient nanoparticulate contrast agent for potential application in multimodal imaging.
Multimodal molecular imaging has recently attracted much attention on disease diagnostics by taking advantage of individual imaging modalities. Herein, we have demonstrated a new paradigm for multimodal bioimaging based on amino acids-anchored ultrasmall lanthanide-doped GdVO4 nanoprobes. On the merit of special metal-cation complexation and abundant functional groups, these amino acids-anchored nanoprobes showed high colloidal stability and excellent dispersibility. Additionally, due to typical paramagnetic behaviour, high X-ray mass absorption coefficient and strong fluorescence, these nanoprobes would provide a unique opportunity to develop multifunctional probes for MRI, CT and luminescence imaging. More importantly, the small size and biomolecular coatings endow the nanoprobes with effective metabolisability and high biocompatibility. With the superior stability, high biocompatibility, effective metabolisability and excellent contrast performance, amino acids-capped GdVO4:Eu(3+) nanocastings are a promising candidate as multimodal contrast agents and would bring more opportunities for biological and medical applications with further modifications.
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