Purpose Magnetoliposomes (MLs) have shown great potential as magnetic resonance imaging contrast agents and as delivery vehicles for cancer therapy. Targeting the MLs towards the tumor cells or neovascularization could ensure delivery of drugs at the tumor site. In this study, we evaluated the potential of MLs targeting the αvβ3 integrin overexpressed on tumor neovascularization and different tumor cell types, including glioma and ovarian cancer. Methods MLs functionalized with a Texas Red fluorophore (anionic MLs), and with the fluorophore and the cyclic Arginine-Glycine-Aspartate (cRGD; cRGD-MLs) targeting the αvβ3 integrin, were produced in-house. Swiss nude mice were subcutaneously injected with 10 7 human ovarian cancer SKOV-3 cells. Tumors were allowed to grow for 3 weeks before injection of anionic or cRGD-MLs. Biodistribution of MLs was followed up with a 7T preclinical magnetic resonance imaging (MRI) scanner and fluorescence imaging (FLI) right after injection, 2h, 4h, 24h and 48h post injection. Ex vivo intratumoral ML uptake was confirmed using FLI, electron paramagnetic resonance spectroscopy (EPR) and histology at different time points post injection. Results In vivo, we visualized a higher uptake of cRGD-MLs in SKOV-3 xenografts compared to control, anionic MLs with both MRI and FLI. Highest ML uptake was seen after 4h using MRI, but only after 24h using FLI indicating the lower sensitivity of this technique. Furthermore, ex vivo EPR and FLI confirmed the highest tumoral ML uptake at 4 h. Last, a Perl’s stain supported the presence of our iron-based particles in SKOV-3 xenografts. Conclusion Uptake of cRGD-MLs can be visualized using both MRI and FLI, even though the latter was less sensitive due to lower depth penetration. Furthermore, our results indicate that cRGD-MLs can be used to target SKOV-3 xenograft in Swiss nude mice. Therefore, the further development of this particles into theranostics would be of interest.
Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50–1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space. Islets were also monitored for two weeks following transplantation through the portal vein of the liver. Hereby, islets labeled with MLs and transplanted under the left kidney capsule were able to correct hyperglycemia and had stable MRI signals until nephrectomy. Interestingly, in vivo MRI of streptozotocin induced diabetic rats transplanted with allogeneic islets demonstrated loss of MRI contrast between 7–16 days, indicative of loss of islet structure. MLs used in this study were not only beneficial for monitoring the location of transplanted islets in vivo with high sensitivity but also reported on islet integrity and hereby indirectly on islet function and rejection.
A common feature in the pathophysiology of different types of diabetes is the reduction of β cell mass and/or impairment of β cell function. Diagnosis and treatment of type 1 and type 2 diabetes is currently hampered by a lack of reliable techniques to restore β cell survival, to improve insulin secretion, and to quantify β cell mass in patients. Current new approaches may allow us to precisely and specifically visualize β cells in vivo and provide viable therapeutic strategies to preserve, recover, and regenerate β cells. In this review, we discuss recent protective approaches for β cells and the advantages and limitations of current imaging probes in the field. Type 1 and Type 2 Diabetes (T1D and T2D) as a β Cell Pathology T1D and T2D, although arising from different etiologies, are each associated with physical and/or functional loss of insulin-secreting β cells [1-3]. T1D is described as a heterogeneous inflammatory disease characterized by infiltration of the pancreatic islets with a number of autoimmune cells (CD4+ and CD8+ T cells, macrophages, dendritic cells, and B cells) [4]. Recent evidence suggests that progression of islet infiltrates promotes β cell dysfunction (reduced first-phase insulin response) and later β cell elimination, which ultimately results in the onset of diabetes. Interestingly, it is now clear that residual β cell mass can be found several years after diagnosis. Thus, a desired strategy for T1D treatment should suppress β cell autoimmunity, along with protection and restoration of the remaining β cell mass. Currently, there are no clinically approved interventional therapies for treating the underlying autoimmunity and boosting β cell survival in T1D. T2D, however, is characterized by insulin resistance following progressive decline in β cell function and accumulation of islet amyloid polypeptide (IAPP, or amylin) in the pancreatic islets [2,5]. The pathology is far more complex, as a recent study on newly diagnosed diabetic subjects postulates a reclassification into five distinct clusters based on the metabolic profile and risk of complications; three of the different cluster are currently considered T2D [6]. The treatment of T2D is mainly limited to metformin monotherapy as the initial strategy to improve insulin sensitivity. When the patient cannot control glycemia by lifestyle and metformin, a pharmacology approach to increase β cell resistance and function will be required, as an alternative to chronic exogenous insulin injections. Highlights Pancreatic β cell failure is characteristic to both T1D and T2D. The JAK-STAT pathway is a promising target to prevent autoimmune β cell destruction. Several strategies are currently being tested to improve insulin production in T2D: preventing β cell death/dysfunction, enhancing β cell proliferation, ameliorating β cell dedifferentiation, and inducing transdifferentiation into β like cells. Imaging and diagnostic tools are required to improve the efficacy of current therapeutic strategies aimed at restoring β cell function. Nanotechnology...
Type 2 diabetes (T2D) is a metabolic disease and a global health crisis. Because of the small mass and high dispersity of beta cells in the pancreas, especially among T2D patients, it remains a tremendous challenge to detect and image beta cell mass (BCM) in vitro and in vivo. Herein, a multimodal nanoprobe is constructed by surface functionalization of magnetic iron oxide nanoparticles with a two-photon fluorescent dye (NaP)-labeled polymer. Owing to the nanoparticle surface energy-transfer effect, the nanoprobe enabled pH-triggered fluorescence/magnetic resonance imaging in the acidic beta cell environment. Specifically, confocal one-photon and two-photon modalities revealed prominent fluorescence in BTC-6 pancreatic beta cells among five major cell types, validating the probe as a sensor for BCM quantification. Kinetic assay, transmission electron microscopy, and viability assay further implicated the probe as a potent inhibitor against the aggregation and toxicity of human islet amyloid polypeptide (IAPP), the peptide associated with T2D. This probe presents a first multimodal theranostic system for imaging BCM and inhibition of beta cell degeneration by IAPP amyloidosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.