Targeted nanoparticle-based drug delivery offers the possibility of overcoming drug toxicity and lack of efficacy and improving drug solubility, stability and delivery. Effective treatment of myocardial ischaemia reperfusion (I/R) injury as a means to prevent heart failure requires targeted delivery of drugs to the site of insult [1]. We have been developing cardiac-targeted drug nanocarriers that are based on fungal hydrophobin proteins. Hydrophobins are small amphipathic proteins found in filamentous fungi and they are able to self-assemble into robust, amphipathic structures and to solubilise hydrophobic compounds [2]. An assessment of the feasibility of utilising the hydrophobin RodA as a targeted drug delivery vehicle specific for ischaemic-reperfused (I/R) myocardium will be presented. Specifically, two RodA variants were employed: RodA-MY, a version of RodA engineered with a peptide sequence CSTSMLKAC reported to bind selectively to I/R myocardium [1] and FITC-RodA, a version of RodA labelled with a single fluorescein group at the N terminus. Wild type RodA and both variants were expressed, purified and able to self-assemble into fibrillar structures. The potential cytotoxicity of RodA was then explored. Cultured rat myocyte-like (H9c2) cells were treated with monomeric and self-assembled forms of RodA. These treatments did not affect H9c2 cell viability or cell cycle profile, indicating that RodA is not cytotoxic. The FITC-labelled RodA was used to analyse the targeting of WT and RodA-MY, using I/R-treated H9c2 cells as a model for I/R myocardium. All of the tested RodA constructs bound to the cells but no selective binding was observed with RodA-MY. Further work will be required to validate this observation and the model of I/R myocardium as well as to optimize display of the targeting peptide. This work lays the foundation for the development of hydrophobins as drug carriers in order to improve the efficacy of therapeutics through site-directed delivery.