Triblock copolymer coated iron oxide nanoparticle conjugate for tumor integrin targeting

Abstract

A key challenge in developing nanoplatform-based molecular imaging is to achieve an optimal pharmacokinetic profile to allow sufficient targeting and to avoid rapid clearance by the reticuloendothelial system (RES). In the present study, iron oxide nanoparticles (IONPs) were coated with a PEGylated amphiphilic triblock copolymer, making them water soluble and function-extendable. These particles were then conjugated with a near-infrared fluorescent (NIRF) dye IRDye800 and cyclic Arginine-Glycine-Aspartic acid (RGD) containing peptide c(RGDyK) for integrin αvβ3 targeting. In vitro binding assays confirmed the integrin-specific association between the RGD-particle adducts and U87MG glioblastoma cells. Successful tumor homing in vivo was perceived in a subcutaneous U87MG glioblastoma xenograft model by both magnetic resonance imaging (MRI) and NIRF imaging. Ex vivo histopathological studies also revealed low particle accumulation in the liver, which was attributed to their compact hydrodynamic size and PEGylated coating. In conclusion, we have developed a novel RGD-IONP conjugate with excellent tumor integrin targeting efficiency and specificity as well as limited RES uptake for molecular MRI.

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery

“…A 1.7-nm spacer showed only weak nonspecific binding, while a 5.7-nm spacer allowed greater access to the deep RGD-binding pocket, resulting in a high degree of specific uptake (FiguRe 4a). RGD peptides conjugated to other NPs have been used to target a v b 3 integrinexpressing tumor cells both in vitro and in vivo for their utility in diagnostic cancer imaging (FiguRe 4b) [82][83][84][85]. The use of RGD peptides to target tumors with iron oxide particles for MRI and PET imaging has also been demonstrated [83].…”

Medical nanoparticles for next generation drug delivery to the lungs

“…Integrin targeting liposomes loaded with doxorubicin inhibited tumour progression in a colon carcinoma mouse model, whereas nontargeting liposomes were ineffective [31]. Several other examples of successful integrin-specific binding of nanoparticles exist [32][33][34]. Another well-known example for targeted drug delivery is the folate receptor that is over-expressed in a variety of tumours [35].…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…Chen et al [337] coated iron oxide nanoparticles obtained from thermal decomposition with a PEGylated amphipilic triblock copolymer consisting of a polybutylacrylate segment, a polyethylacrylate segment, a polymethacrylic acid segment and a hydrophobic hydrocarbon side chain, to make them water soluble and function-extendable. [338] They were also conjugated with peptides and imaging moieties which consequently showed excellent tumor targeting efficiency, relatively long circulation half-life and limited liver macrophage uptake.…”