Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O -CNN), and compared them with nitrogen CNN (N -CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O , 5% CO and 74% N ) and their protective effects during hypoxia (1% O , 5% CO and 94% N ) and reoxygenation (21% O , 5% CO and 74% N ) were studied. Neither O -CNN nor N -CNN has any effect on the growth curve during normoxia. However, O -CNN applied before hypoxia induces a 15-30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N -CNN. O -CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.