Gold nanoparticles (GNPs) have garnered significant attention in biomedical applications, particularly as versatile platforms for drug delivery and targeted therapy. The conjugation of GNPs with antibodies offers a promising strategy to enhance their specificity and efficacy in various therapeutic approaches. In this study, we focus on synthesizing different types of GNPs conjugated with antibodies and investigate the influence of various synthesis methods on nanoparticle characterization. The results demonstrated that different synthesis methods lead to different degrees of antibody conjugation on the GNP surface and to varied efficiency on biosystems. This work has the potential to outline design principles that could positively affect the development of targeted nanotherapeutics for various biomedical applications.
Delivery of therapeutics to tumors is a major challenge, due to the sequence of formidable biological barriers in the body and tumor, which limit the penetration of various nano-carriers and drugs into the tumor. Exosomes are promising vectors for delivery of anti-tumor therapies, due to their biocompatibility, ability to evade clearance, and innate ability to home to, and interact with, target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome bio-distribution, tumor targeting, and the ability to overcome tumor barriers. Here, we examined these parameters using mesenchymal stem cell (MSCs)-derived exosomes loaded with gold nanoparticles (GNPs), aiming to delineate design principles for therapy loading and delivery. This novel technology provides essential and fundamental knowledge on exosomes for enhanced targeted drug delivery to tumors, and has potential to promote clinical translation of exosome-based cancer therapy.
Liposomes are a promising drug delivery system, owing to their biocompatibility and ability to efficiently encapsulate and protect a wide range of molecules for medical applications. Active targeting of the liposomes is typically performed by surface modification, which enables delivery of the liposomes to a specific target tissue. Tumor cells are characterized by high glucose demand and high metabolic activity, because of the increased requirement of energy to feed uncontrolled proliferation. Taking advantage of the increased glucose uptake by cancer cells, we developed a glucose-labeled liposome, which is tumor-targeted - both by recognition of over-expressed glucose transporters on tumor cells, and by the unique characteristics of tumor vasculature that allow greater accumulation of nanoparticles. In this study, glucosecoated liposome uptake was evaluated in different types of cancer cells, both quantitatively and qualitatively. We found that liposomes with glucose coating were preferentially uptaken by cancer cell lines with high metabolic activity, compared to liposomes without glucose coating. Moreover, cell lines with high metabolic activity exhibited higher uptake of liposomes with glucose coating, as compared to cell lines with low metabolic activity and to non-cancerous cell lines.
Gold nanoparticles (GNPs) are becoming an increasingly prominent biomedical tool. GNPs are biocompatible and can carry high payloads and a wide array of biological materials, making them an ideal delivery vector for various therapeutics, such as gene therapy. However, one major obstacle to clinical application is endosomal entrapment and subsequent degradation of the nanoparticletherapy complex. Coating GNPs with an endosomal escape agent can serve as an effective approach to overcome this challenge. This study explores the probability of different types of coated GNPs to perform endosomal escape. We used a novel, multi-modal approach applying fluorescent confocal microscopy, as well as sophisticated image analysis, to provide a quantitative and uniform method that can denote endosomal escape efficacy. Our findings can ultimately advance understanding of endosomal escape abilities of various GNP coatings and promote their application for gene therapy.
Bacterial infection and biofilm buildup is a major challenge for wound healing. In the present work we developed a method to track bacteria in vivo in order to analyze the progress of the healing. Regulated irrigation combined with negative pressure (RI-NPT) is a nonpharmaceutical therapeutic strategy for reducing bacterial load in acute and chronically infected wounds. Here, we analyzed RI-NPT hydrokinetics and efficacy of bacterial load reduction in wounds. Escherichia coli were loaded with gold nanoparticles, in order to make them "visible" and trackable using computed tomography (CT). Bacteria were tracked using CT in a low-flow rat wound model over time. CT tracking revealed that while regulated negative pressure-assisted wound therapy reduced bacterial load to a limited extent (5%), RI-NPT significantly increased bacterial outflow and clearance (by 45%). This nanotechnology-based approach demonstrates the ability to track bacteria in vivo at real time and also the ability of the RI-NPT technology to effectively reduce bacterial load.
Cell replacement therapy is a feasible approach for vision restoration in several degenerative diseases of the outer retina in order to halt disease progression and recover lost vision. In this treatment photoreceptor precursors are transplanted in the subretinal space and later integrate within the retina. In order to evaluate the efficiency of cell transplantation for vision restoration, it is crucial to monitor cell survival and integration in the host retina over extended periods, therefore, longitudinal tracking of the transplanted cells in clinical and experimental setups is crucial. Here we present a technique for labeling photoreceptor precursors with gold nanoparticles prior to vitreous and subretinal space transplantation treatment. This labeling allow multimodal imaging using both computed tomography (CT), optical coherence tomography(OCT) and fluorescence fundus imaging. Our multimodal imaging technique enabled high-resolution longitudinal tracking of the transplanted cells for over a month, and quantification of cell survival in the retina and vitreous, without any toxic effects. These findings promote the use of nanoparticles for retinal cell tracking and its translational potential providing more efficient cell replacement therapies for clinical applications.
KEYWORDS: Nanoparticles, Iron, Magnetic resonance imaging, Gold, Computed tomography, Particles, In vivo imaging, Transmission electron microscopy, Molecules
Multimodal imaging, integrating different imaging modalities, is emerging as a promising strategy for improving both preclinical and clinical imaging. Computed tomography (CT) and magnetic resonance imaging (MRI) are among the widely clinically-used imaging techniques. These imaging modalities are used for disease diagnosis and screening, each providing different and complementary information about the patient and the disease state. Nanoparticles are considered promising contrast agents for in vivo imaging applications, providing improved imaging and targeting capabilities compared to the commonly used contrast compounds. In this project, we present the development of a novel hybrid nanostructure, comprising of iron oxide core and gold shell nanoparticle for dual model CT and MRI imaging. The hybrid structures presented herein have potential to serve as a unique platform for precision imaging.
Nanomaterials functionalized with glucose have shown a great potential in cancer diagnosis and treatment. We have recently demonstrated that gold nanoparticles (GNP), functionalized with glucose, can be used for specific and sensitive tumor detection when combined with computed tomography (CT) - GNP functionalized with glucose in the second carbon position were used as a metabolically targeted contrast agents, and were able to discriminate between cancer and inflammation, which is a superior ability when comparing the FDG-PET which is not tumor specific. Here we aim to understand the uptake mechanisms of the glucose functionalized GNP using a comprehensive in vitro study in several cell types with different metabolic features, and examining the glucose transporter-1 (GLUT1) involvement in the uptake process. We found that the glucose functionalized GNP are not toxic to the cells in the tested concentrations and we demonstrate that the cellular uptake of GNP, when functionalized with glucose in the second carbon position, strongly depends on GLUT1 expression in the cells, which triggers clathrin-mediated endocytosis of the nanoparticles. This study can promote control and development of glucose-functionalized nanoparticles for many biological applications.
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