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Fig. 1 Synthesis of cardiac-homing lipid nanoparticles. (a) Reaction between protein reactive pairs to generate a modular artificial membrane-binding protein (AMBP). Protein fusion 1, consisting of SpyCatcher (SC3, shown in blue) and supercharged green fluorescent protein (scGFP, shown in green), reacts bioorthogonally with protein fusion 2, consisting of SpyTag (ST3, shown in blue), mCherry (mCh, shown in red), and the fibronectin-binding protein CshA (shown in yellow), forming an isopeptide bond through the side chains of SC3 Lys28 and ST3 Asp10. An additional protein fusion 3, consisting of mCh and ST3 was generated as a negative control of cardiac homing. Other negative controls were protein fusions 4, consisting of cardiac-homing protein CshA fused to the scGFP-anchoring domain, and 5, consisting of just the anchoring domain. (b) Cardiac-homing (CH) lipid nanoparticle (LNP), 1:2-LNP, is ensembled upon mixing of the modular AMBP and our in-house LNPs made of cholesterol (CHOL, 58% v/v), 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, 22% v/v), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, 16% v/v), and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS, 8% v/v). The figure was created using BioRender.com.