Dual-Stimuli-Responsive, Polymer-Microsphere-Encapsulated CuS Nanoparticles for Magnetic Resonance Imaging Guided Synergistic Chemo-Photothermal Therapy

Integrating biomedical imaging and multimodal therapies into one platform for enhanced anticancer efficacy is of great significance. Herein, a core/shell structured nanotheranostic (CuS@copolymer) for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy was simply prepared via emulsifier-free emulsion polymerization with the full participation of hydrophilic CuS NPs, styrene (St), N-isopropylacrylamide (NIPAm), methacrylic acid (MAA), and polymerizable rare earth complex (Gd(AA)₃phen). The synthesized multifunctional microspheres with excellent biocompatibility exhibited high loading capacity (15.3 wt %) for DOX·HCl and excellent drug release under low pH and high temperature. The photosensitive CuS cores which can simultaneously efficiently absorb near-infrared (NIR) light and convert NIR light to fatal heat, leading to a synergistic therapeutic effect combined photothermal therapy (PTT) with chemotherapy. Moreover, the temperature sensitive copolymer attached onto the CuS nanoparticles was able to be productively infected by the thermal effect and give rise to a highly controllable DOX release. Furthermore, the CuS@copolymer/DOX showed an enhanced therapeutic efficacy against 4T1 cells than separate photothermal therapy or chemotherapy. Additionally, the drug delivery procedure could be visualized by in vivo MR images and the longitudinal relaxivity (r₁) was calculated to be 10.72 mM^–1 s^–1. These results suggest the CuS@copolymer microspheres highly attractive candidates for biomedical applications.