Aim: To develop biocompatible and bioresorbable negatively charged calcium phosphate nanoparticles (CaP-NPs) as an innovative therapeutic system for the delivery of bioactive molecules to the heart. Materials & methods: CaP-NPs were synthesized via a straightforward one-pot biomineralization-inspired protocol employing citrate as a stabilizing agent and regulator of crystal growth. CaP-NPs were administered to cardiac cells in vitro and effects of treatments were assessed. CaP-NPs were administered in vivo and delivery of microRNAs was evaluated. Results: CaP-NPs efficiently internalized into cardiomyocytes without promoting toxicity or interfering with any functional properties. CaP-NPs successfully encapsulated synthetic microRNAs, which were efficiently delivered into cardiac cells in vitro and in vivo. Conclusion: CaP-NPs are a safe and efficient drug-delivery system for potential therapeutic treatments of polarized cells such as cardiomyocytes.