Development of Folate‐Superparamagnetic Nanoconjugates for Inhibition of Cancer Cell Proliferation

Abstract Here, a versatile strategy to engineer smart theranostic nanocarriers is reported. The core/shell nanosystem is composed of a superparamagnetic iron oxide (Fe_3−δO₄) nanoparticle (NP) core bearing the biocompatible thermo‐responsive poly(2‐(2‐methoxy)ethyl methacrylate‐oligo(ethylene glycol methacrylate), P(MEO₂MA_x‐OEGMA_100−x) copolymer (where x and 100‐x represent the molar fractions of MEO₂MA and OEGMA, respectively). Folic acid (FA) is end‐conjugated to the P(MEO₂MA_x‐OEGMA_100−x) copolymer, leading to Fe₃−_δO₄@P(MEO₂MA_x‐OEGMA_100−x)‐FA, to facilitate active targeting of NPs to cancer cells. A highly potent hydrophobic anticancer agent doxorubicin (DOX) is incorporated in the thermo‐responsive P(MEO₂MA_x‐OEGMA_y) brushes via supramolecular interactions to increase its solubility and the assessment of therapeutic potentials. These experiments confirm the magnetic hyperthermia properties of nanocarrier and reveal that only a small amount (10% ± 4%) of DOX is diffused at room temperature, while almost full drug (100%) is released after 52 h at 41 °C. Interestingly, it is found that P(MEO₂MA₆₀‐OEGMA₄₀) polymers offer to NPs a promising stealth behavior against Human Serum Albumin and Fibrinogen model proteins.