Breast cancer remains one of the most prevalent and lethal malignancies in women. The inability to diagnose small volume metastases early has limited effective treatment of stage 4 breast cancer. Here we report the rational development and use of a multifunctional superparamagnetic iron oxide nanoparticle (SPION) for targeting metastatic breast cancer in a transgenic mouse model and imaging with magnetic resonance (MR). SPIONs coated with a copolymer of chitosan and polyethylene glycol (PEG) were labeled with a fluorescent dye for optical detection and conjugated with a monoclonal antibody against the neu receptor (NP-neu). SPIONs labeled with mouse IgG were used as a non-targeting control (NP-IgG). These SPIONs had desirable physiochemical properties for in vivo applications such as near neutral zeta potential and hydrodynamic size around 40 nm, and were highly stable in serum containing medium. Only NP-neu showed high uptake in neu expressing mouse mammary carcinoma (MMC) cells which was reversed by competing free neu antibody, indicating their specificity to the neu antigen. In vivo, NP-neu was able to tag primary breast tumors and significantly, only NP-neu bound to spontaneous liver, lung, and bone marrow metastases in a transgenic mouse model of metastatic breast cancer, highlighting the necessity of targeting for delivery to metastatic disease. The SPIONs provided significant contrast enhancement in MR images of primary breast tumors; thus, they have the potential for MRI detection of micrometastases, and provide an excellent platform for further development of an efficient metastatic breast cancer therapy.

Nanoparticle-based cancer therapeutics promises to improve drug delivery safety and efficacy. However, fabrication of consistent theranostic nanoparticles with high and controllable drug loading remains a challenge, primarily due to the cumbersome, multi-step synthesis processes conventionally applied. Here, we present a simple and highly controllable method for assembly of theranostic nanoparticles, which may greatly reduce batch-to-batch variation. The major components of this nanoparticle system include a superparamagnetic iron oxide nanoparticle (SPION), a biodegradable and pH-sensitive poly (beta-amino ester) (PBAE) copolymer, a chemotherapeutic agent doxorubicin (DOX). Here the polymer pre-loaded with drug is directly assembled to the surface of SPIONs forming a drug loaded nanoparticle (NP-DOX). NP-DOX demonstrated a high drug loading efficiency of 679 µg DOX per mg iron, sustained stability in cell culture media up to 7 days, and a strong r2 relaxivity of 146 mM−1•s−1 for magnetic resonance imaging (MRI). The drug release analysis of NP-DOX showed fast DOX release at pH 5.5 and 6.4 (as in endosomal environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release kinetics. In vitro evaluation of NP-DOX efficacy using drug-resistant C6 glioma cells showed a 300% increase in cellular internalization at 24 h post-treatment and 65% reduction of IC50 at 72 h post-treatment when compared to free DOX. These nanoparticles could serve as a foundation for building smart theranostic formulations for sensitive detection through MRI and effective treatment of cancer by controlled drug release.

The presumed pathophysiology of isolated neuroleukemiosis is hematogenous spread of leukemic cells into the peripheral nervous system across the blood-nerve barrier. It should be considered in the differential diagnosis in patients with leukemia who present with neuropathy, even when they are considered to be clinically cured of leukemia.