Engineering magnetic-molecular sequential targeting nanoparticles for anti-cancer therapy

Nanoparticle drug delivery to tumors via the enhanced permeability and retention (EPR) effect is usually limited by the step of blood circulation and extravasation. Only less than 10% of the administered dose would eventually reach the tumor tissue. To enhance the drug delivery efficiency, we report the approach of magnetic plus molecular dual targeting nanoparticles to combine tumor targeting, drug delivery, and in situ imaging together. The surface of superparamagnetic iron oxide nanoparticles (SPIONs) was coated with biocompatible poly(ethylene glycol)-poly(lactic acid) and then anchored with folic acid (FA). Despite the presence of FA, the hydrodynamic size of SPIONs was less than 100 nm. Increasing the surface FA density sacrificed the aqueous stability of SPIONs, but 20% FA did not induce noticeable particle aggregation. The existence of 20% FA maintained the superparamagnetic property of SPIONs with a saturation magnetization level at ca. 30 emu g^-1. The drug release profile was not significantly different between SPIONs with (20%) and without FA. However, the presence of FA dramatically increased the intracellular uptake of SPIONs when using the MCF-7 breast cancer cell line. These results highlighted the role of surface ligand optimization in the design of desired magnetic-molecular dual tumor-targeting nanoparticles.