Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Abstract

Background The significant progress in nanotechnology provides a wide spectrum of nanosized material for various applications, including tumor targeting and molecular imaging. The aim of this study was to evaluate multifunctional liposomal nanoparticles for targeting approaches and detection of tumors using different imaging modalities. The concept of dual-targeting was tested in vitro and in vivo using liposomes derivatized with an arginine-glycine-aspartic acid (RGD) peptide binding to α v β 3 integrin receptors and a substance P peptide binding to neurokinin-1 receptors. Methods For liposome preparation, lipids, polyethylene glycol building blocks, DTPA-derivatized lipids for radiolabeling, lipid-based RGD and substance P building blocks and imaging labels were combined in defined molar ratios. Liposomes were characterized by photon correlation spectroscopy and zeta potential measurements, and in vitro binding properties were tested using fluorescence microscopy. Standardized protocols for radiolabeling were developed to perform biodistribution and micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies in nude mice bearing glioblastoma and/or melanoma tumor xenografts. Additionally, an initial magnetic resonance imaging study was performed. Results Liposomes were radiolabeled with high radiochemical yields. Fluorescence microscopy showed specific cellular interactions with RGD-liposomes and substance P-liposomes. Biodistribution and micro-SPECT/CT imaging of 111 In-labeled liposomal nanoparticles revealed low tumor uptake, but in a preliminary magnetic resonance imaging study with a single-targeted RGD-liposome, uptake in the tumor xenografts could be visualized. Conclusion The present study shows the potential of liposomes as multifunctional targeted vehicles for imaging of tumors combining radioactive, fluorescent, and magnetic resonance signaling. Specific in vitro tumor targeting by fluorescence microscopy and radioactivity was achieved. However, biodistribution studies in an animal tumor model revealed only moderate tumor uptake and no additive effect using a dual-targeting approach.

Multifunctional calcium phosphate nanoparticles for combining near-infrared fluorescence imaging and photodynamic therapy

“…Among them, RGD peptides are particularly suitable for enhancing intratumoral probe enrichment. RGD peptides specifically bind to a v b 3 integrins on the activated endothelium of angiogenic blood vessels, they can easily be conjugated to nanoparticles and they are cheaper than antibodies [17][18][19][20].…”

Design and Applications of Bispecific Heterodimers: Molecular Imaging and beyond

“…108 However, molecular imaging research with those types of bispecific nanomaterials is extremely limited, and so far, there is only one report using a bispecific liposome to target integrin α v β 3 and neurokinin-1 receptor in glioblastoma. 109 Unfortunately, there was no observable tumor-uptake enhancement compared with that of an unconjugated liposome in this study, which was monitored by SPECT/CT (Figure 4A). However, bispecific ligand-modified nanomaterials have also generated various exciting results.…”

Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P

“…Cellular experiments with SP derivatives have been conducted following methods described previously (Rangger et al, 2013). U-87MG cells (CLS Cell Lines Service, Eppelheim, Germany) were removed from the original medium using a procedure suggested by the supplier and subcultured in Erlenmeyer tissue culture flasks (Dispomeyer, VWR International PBI, Milan, Italy) using Dulbecco's modified Eagle medium (DMEM) supplemented with 10% volume/ volume (v/v) heat-inactivated fetal bovine serum, 1% v/v penicillin/ streptomycin/L-glutamine solution, 1% v/v sodium pyruvate solution, and 1% v/v non-essential amino acid solution (NEAA).…”