Coupling of HPLC with Electrospray Ionization Mass Spectrometry for Studying the Aging of Ultrasmall Multifunctional Gadolinium-Based Silica Nanoparticles

Sub-5 nm multimodal nanoparticles have great potential for theranostic applications due to their easy renal elimination combined with complementary imaging properties and therapeutic facilities. Their potential clinical use requires the full characterization of not only the nanoparticle but also all its possible degradation products. We have recently proposed new ultrasmall gadolinium-based nanoparticles for multimodal imaging and radiosensitization. The aim of this article is to describe an analytical tool to characterize degradation products in a highly diluted medium. We demonstrate that HPLC coupled to electrospray ionization mass spectrometry (ESI-MS) can be used in order to determine precisely the composition of nanoparticles and their degradation fragments during aging

Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Resonance–Computed Tomography Image Guided Radiation Therapy

Selective killing of cancer cells while minimizing damage to healthy tissues is the goal of clinical radiation therapy. This therapeutic ratio can be improved by image-guided radiation delivery and selective radiosensitization of cancer cells. Here, we have designed and tested a novel trimodal theranostic nanoparticle made of bismuth and gadolinium for on-site radiosensitization and image contrast enhancement to improve the efficacy and accuracy of radiation therapy. We demonstrate in vivo magnetic resonance (MR), computed tomography (CT) contrast enhancement, and tumor suppression with prolonged survival in a non-small cell lung carcinoma model during clinical radiation therapy. Histological studies show minimal off-target toxicities due to the nanoparticles or radiation. By mimicking existing clinical workflows, we show that the bismuth–gadolinium nanoparticles are highly compatible with current CT-guided radiation therapy and emerging MR-guided approaches. This study reports the first in vivo proof-of-principle for image-guided radiation therapy with a new class of theranostic nanoparticles

High-Resolution Cellular MRI: Gadolinium and Iron Oxide Nanoparticles for in-Depth Dual-Cell Imaging of Engineered Tissue Constructs

Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to “tattoo” endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells’ contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both <i>in vitro</i> and <i>in vivo</i>. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components

Functionalization of Small Rigid Platforms with Cyclic RGD Peptides for Targeting Tumors Overexpressing α_vβ₃‑Integrins

Gadolinium based Small Rigid Plaforms (SRPs) have previously demonstrated their efficiency for multimodal imaging and radiosensitization. Since the RGD sequence is well-known to be highly selective for α_vβ₃ integrins, a cyclic pentapeptide containing the RGD motif (cRGDfK) has been grafted onto the SRP surface. An appropriate protocol led to the grafting of two targeting ligands per nano-object. The resulting nanoparticles have demonstrated a strong association with α_vβ₃ integrins in comparison with cRADfK grafted SRPs as negative control. Flow cytometry and fluorescence microscopy have also been used to highlight the ability of the nanoparticles to target efficiently HEK293­(β3) and U87MG cells. Finally the grafted radiosensitizing nanoparticles were intravenously injected into <i>Nude</i> mice bearing subcutaneous U87MG tumors and the signal observed by optical imaging was twice as high for SRP-cRGDfK compared to their negative analogue