Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

Abstract

A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

Radio‐Labeled Nanoparticles for Biomedical Imaging

“…bps are drugs that bind strongly to metabolically active bone as used in oncology and osteoporosis [62]. bp can be further functionalized with fluorophores, radionuclides, and biological tags, thus serving as anchor agents on SpIONs [63][64][65]. A clinically approved, SpIO-based liver mRI agent, endorem/feridex, was conjugated to a 99m Tc-bp tracer via the dipicolylamine-alendronate (DpA-ale) group.…”

“…Liposomes radiolabeled with 64 Cu were used to probe the enhanced permeability and retention (epR) effect in tumor-bearing mice. In this study, a remote loading approach was employed to encapsulate 64 Cu into liposomes to achieve improved radiolabeling stability and tumor accumulation (5.0 ± 2.0% ID/organ) [90].…”

“…In this study, a remote loading approach was employed to encapsulate 64 Cu into liposomes to achieve improved radiolabeling stability and tumor accumulation (5.0 ± 2.0% ID/organ) [90]. Due to the long in vivo half-life (t 1/2 = 18 h), high tumor-to-muscle ratio (17.9 ± 8.1) was achieved with these 64 Cu-liposomes. In contrast to a small-molecule-based radiotracer of 124 I-SKI212243 targeting egfR kinase, 124 I-SKI212243-conjugated liposomes showed significantly higher tumor accumulation (three-to six-fold increase) at 48 h p.i.…”

“…To date, radiolabeling strategies resulting in high labeling yield and specific activity have been established for labeling iron oxide nanoparticles with positron emitters such as 64 Cu, 68 ga, and 124 I. The in vivo biodistribution and targeting efficiency of these radiolabeled nanoparticles have been studied in a variety of animal disease models [95][96][97][98].…”

New dextrin nanomagnetogels as contrast agents for magnetic resonance imaging

“…[2][3][4][5] In addition, MNPs have been recognized as a promising tool for site-specic delivery of drugs and of diagnostic agents through the application of an external magnetic eld.…”