Liposomes with embedded magnetic nanoparticles (magnetoliposomes; MLs) are promising nano-platforms for various biomedical applications. The magnetic behavior of MLs depends on the size of embedded magnetic nanoparticles (MNPs); in general, larger MNPs are more advantageous (e.g. increased magnetic signals). However, the insertion of large MNPs into liposome bilayers is constrained by the thickness of the membrane (∼3.4 nm); thus, the incorporation of larger magnetic nanoparticles (>3.4 nm) into liposomes is a major challenge. We developed a solvent-guided approach for the simple and efficient insertion of large MNPs (6 nm or 15 nm) into the liposomal bilayer. MLs with 6 nm MNPs were used for the magnetic field-guided separation of cancer cells by targeting to human epidermal receptor 2 and folate receptor. We also evaluated the nuclear delivery of oligonucleotides by MLs with a cationic lipid formula. The MLs are expected to be versatile nano-platforms for biomedical applications (e.g. disease diagnosis, therapeutics and cell tracking).