Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting

Abstract

Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles (SPIOs) and apply pulsed magnetic-field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumors, resulting in increased tumour macrophage infiltration and reduction in tumor burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues.

Progress in tumor-associated macrophage (TAM)-targeted therapeutics

“…A study by Chang and Guo et al shows that the size of nanoparticles internalized by macrophages can significantly alter locomotivity of the macrophages, with smaller nanoparticles (30 and 50 nm) having higher uptake into macrophages than larger nanoparticles (100 and 500 nm) but also more readily retarding the migration rate of the macrophages; this study suggests that 100 nm nanoparticles provide a good balance for effective drug loading and macrophage migration [174]. To increase control over drug activity from macrophage carriers, macrophage have been loaded with temperature-responsive liposomes for triggered release [216], with gold-silica nanoshells for photothermal therapy [215], and with iron oxide nanoparticles for dual tracking and trafficking using electromagnetic actuation [214][222][223]. …”

Delivering safer immunotherapies for cancer

“…injection, a pulsed magnetic field gradient was applied by MRI to provide a magnetic force promoting accumulation of the iron-loaded macrophages at primary or metastatic tumor sites, leading to a ~6-fold increase in donor cell accumulation throughout tumors. While injection of free oncolytic virus led to only minor inhibition of tumor growth, substantial sustained tumor growth blockade was achieved through magnetic field-mediated targeting of iron oxide-loaded infected macrophages to tumors [261]. …”

A Laser-Activated Biocompatible Theranostic Nanoagent for Targeted Multimodal Imaging and Photothermal Therapy

“…The shell surface was modified with polyethylene glycol (PEG) to prolong blood circulation time and HER2 targeting ligands for targeting HER2 expressing cancer cells. Superparamagnetic iron oxide (SPIO) nanoparticles [32] within the shell enable MR [33][34][35] and PA [36] imaging. Also contained in the shell is 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyan ine iodide (DIR), commonly used as a NIRF contrast agent [37].…”