Poly(ethylene glycol)-alendronate coated nanoparticles for magnetic resonance imaging of lymph nodes

Abstract

Nanoparticulate systems can passively target regional lymphatic vessels and lymph nodes (LNs) after interstitial administration. Highly sensitive non-invasive imaging techniques, such as magnetic resonance imaging (MRI), can take advantage from particles' lymphotropic properties to provide a reliable tool to monitor lymphatic function and LN morphology with high spatial resolution. In this work, we developed and characterised a bioerodible nanosystem with MRI contrast properties, based on poly(ethylene glycol)-alendronate stabilised gadolinium calcium phosphate nanoparticles (NPs). After foot paw injection in mice, the particles exhibited a distinct pattern of gradual uptake into the local lymphatics and a localised deposition in the popliteal LN. Less variability in the onset of the signal, intensity and localisation was observed compared to the commercially available tracer gadobutrol, suggesting that these NPs could be useful to monitor physiological and dysfunctional lymphatic conditions. Moreover, dissolution of the particles indicated that they would be rapidly cleared from the body after imaging. Nevertheless, our findings call for an improvement of the system that includes reduction of gadolinium leakage from the NPs, and decrease in size of the latter to increase their selective uptake by the LN.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma

“…Nevertheless, the low molecular weight of gadolinium-based contrast agents result in rapid lymphatic transportation, little retention in SLNs and rapid washout of the contrast agent [ 46 , 91 ]. This could increase the risk to overlook SLNs and of contrast-enhanced HEN(s) to erroneously being considered SLN(s).…”

Nanotechnologies for Physiology-Informed Drug Delivery to the Lymphatic System

“…Traditional contrast agents are administered via intravenous injection, which results in low specificity and sensitivity to visualize lymphatic vessel structures. Recently, a calcium phosphate nanoparticle coated with PEG-alendronate and loaded with a contrast agent was developed to test its enhancement of lymphatic system visualization under magnetic resonance imaging (MRI) ( 90 ). They found that contrast efficiency of the nanoparticle formulation was 1.6-fold higher than that of the control free contrast agent solution.…”

Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

“…On the other hand, a lower transfection was observed after administration of the naked plasmid, suggesting that pDNA incorporation in NPs increases the degree of DNA transfer efficiency across the cell membrane. However, the low in vivo transfection efficacy of the PEGma-Ale coated CaP NPs could be potentially explained by a lower pDNA dose compared to those found in the literature [56], a lower particle uptake in vivo (due to the absence of a sedimentation effect) and/or to the premature CaP dissolution (and subsequent extracellular pDNA release) that may occur under dilute conditions [57]. Moreover, particles aggregation at the injection site and/or poor diffusion through the extracellular matrix could also have impaired the transfection ability of the system.…”