Herceptin-Conjugated DOX-Fe3O4/P(NIPAM-AA-MAPEG) Nanogel System for HER2-Targeted Breast Cancer Treatment and Magnetic Resonance Imaging

Abstract

It is essential to synthesize a "diagnosis and therapy" integration nanocarrier for magnetic resonance imaging-guided breast cancer-targeted chemotherapy. Here, we report Fe3O4/P(NIPAM-AA-MAPEG) nanogels (MNLs) based on in situ loading of doxorubicin (DOX) by miniemulsion polymerization. Especially, propyl acrylic acid (AA) moieties were introduced to absorb DOX by electrostatic interactions and conjugated with the antibody herceptin (HER) through the amino-carboxyl coupling reaction. The size and morphology of MNLs could be adjusted by varying the polymerization parameters, such as the monomer feeding ratio, ferrofluid content, and cross-linker content. The MNLs showed superior stability in a physiological environment, but their structures were destroyed in an acidic environment to accelerate DOX release. The dissociation of the HER-DOX-MNLs accelerated the delivery of DOX and enhanced the therapeutic effects. The studies exhibited that the HER-DOX-MNLs could inhibit the tumor growth. In addition, the MNLs with a high magnetic content had the potential advantages in magnetic resonance imaging (MRI) of breast cancer diagnosis. The dual-targeted pH-responsive nanogels were successfully designed as a multifunctional nanocarrier for realizing HER2-positive breast cancer chemotherapy and diagnostics.