Antibody-directed metal-organic framework nanoparticles for targeted drug delivery

Abstract

Nanosized metal-organic frameworks (nMOFs) have shown great promise as high-capacity carriers for a variety of applications. For biomedicine, numerous nMOFs have been proposed that can transport virtually any molecular drug, can finely tune their payload release profile, etc. However, perspectives of their applications for the targeted drug delivery remain relatively unclear. So far, only a few works have reported specific cell targeting by nMOFs exclusively through small ligands such as folic acid or RGD peptides. Here we show feasibility of targeted drug delivery to specific cancer cells in vitro with nMOFs functionalized with such universal tool as an antibody. We demonstrate ca. 120 nm magnetic core/MOFs shell nanoagents loaded with doxorubicin/daunorubicin and coupled with an antibody though a hydrophilic carbohydrate interface. We show that carboxymethyl-dextran coating of nMOFs allows extensive loading of the drug molecules (up to 15.7 mg/g), offers their sustained release in physiological media and preserves antibody specificity. Reliable performance of the agents is illustrated with trastuzumab-guided selective targeting and killing of HER2/neu-positive breast cancer cells in vitro. The approach expands the scope of nMOF applications and can serve as a platform for the development of potent theranostic nanoagents. STATEMENT OF SIGNIFICANCE: The unique combination of exceptional drug capacity and controlled release, biodegradability and low toxicity makes nanosized metal-organic frameworks (nMOFs) nearly ideal drug vehicles for various biomedical applications. Unfortunately, the prospective of nMOF applications for the targeted drug delivery is still unclear since only a few examples have been reported for nMOF cell targeting, exclusively for small ligands. In this work, we fill the important gap and demonstrate nanoagent that can specifically kill target cancer cells via drug delivery based on recognition of HER2/neu cell surface receptors by such universal and specific tool as antibodies. The proposed approach is universal and can be adapted for specific biomedical tasks using antibodies of any specificity and nMOFs of a various composition.

Keywords: Cancer cell targeting; Core-shell hybrid structures; Daunorubicin; Doxorubicin; HER2/neu; MIL-100; Magnetic nanoparticles; Targeted drug delivery; Theranostics.