Liposomes, self-assembled lipid-based nanoparticles, have gained significant attention due to their versatility and potential applications in various biomedical fields. They serve as promising platforms for targeted drug delivery, imaging, and therapeutics. Among the various types of liposomes, radiolabeled liposomes have attracted considerable interest due to their unique capabilities in both therapy and imaging. In therapy, radiolabeled liposomes can effectively transport therapeutic radioactive agents directly to disease sites, allowing for precise and localized treatment. In imaging, radiolabeling enables non-invasive visualization and tracking of liposomes, providing valuable diagnostic information. In this study, we present a technique for surface radiolabeling of liposomes, achieved by introducing a chelating agent onto the liposome surface and optimizing radiolabeling conditions for desired radionuclides. Importantly, our technique allows for the radiolabeling process to be conducted after the liposomes have been formulated according to the desired composition, enabling seamless integration into biomedical research and clinical practice. Our research investigates optimal radiolabeling conditions for different isotopes, ensuring stability and high efficiency. Purification and characterization of the resulting radiolabeled liposomes validate their quality and stability. The findings of this study offer valuable insights for the future advancement and application of radiolabeled liposomes in biomedical research and clinical practice, holding promise for improved therapies and diagnostics.
Cisplatin (CP) is the primary standard treatment for bladder cancer. Nevertheless, CP has side effects, particularly nephrotoxicity. This limits the treatment of a notable portion of advanced bladder cancer patients with cisplatin. We have developed gold nanoparticles that conjugate CP (CP-AuNPs) for safer delivery to tumors. Here, we investigated the biodistribution of the CP-AuNP conjugates in a mouse model of bladder cancer, to characterize the distinct role of CPAuNP in delivering and releasing CP in tumor and tissues. Effect of the CP-AuNPs on weight and kidney was also investigated. This study can provide insights into the potential safety of CP-AuNP for bladder cancer treatment.
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.
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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