Zwitterionic Polymer-Gated Au@TiO₂ Core-Shell Nanoparticles for Imaging-Guided Combined Cancer Therapy

With advances in nanoparticle (NP) synthesis and engineering, nanoscale agents with both therapeutic and diagnostic functions have been increasingly exploited for cancer management. Herein, we synthesized a new type of zwitterionic polymer-gated Au@TiO₂ core-shell nanoparticles, which showed that they could selectively target and efficiently eliminate cancer cells via photothermal therapy (PTT), photodynamic therapy (PDT), pH/NIR-induced drug release, and cationic therapy. Methods: In the present study, the multifunctional therapeutic agent [Mn@P(CitAPDMAEMA)@Au@TiO₂@DOX] was prepared to treat cancer with imaging-guided combination method. Firstly, Au@TiO₂ core-shell nanoparticles (NPs) were synthesized. Taking advantage of broad and strong photoabsorption and reactive oxygen species (ROS) generation, Au@TiO₂ core-shell NPs facilitated the single light-induced PTT and PDT. Next, a chemotherapy drug doxorubicin (DOX) was loaded into Au@TiO₂ core-shell NPs. Then, a biocompatible zwitterionic polymer P(CitAPDMAEMA) was grafted to improve the hemocompatibility of NPs and prolong the circulation time. The polymer also served as a capping or switching material for pH-triggered drug release. In addition, the cationic nature of P(CitAPDMAEMA) eased the binding to human cervical cancer (HeLa) cells and effectively inhibited their growth in acidic environments (termed cationic therapy). Moreover, with Mn²⁺ ions immanently chelated, Mn@P(CitAPDMAEMA)@Au@TiO₂@DOX NPs were able to provide enhanced contrast under T₁- or T₂-weighted magnetic resonance imaging (MRI). Results: The in vitro and in vivo anticancer experiments demonstrated the tumor was effectively inhibited with minimal side effects by the multifunctional NPs. Conclusions: As far as we know, this is the first presentation of four therapeutic methods into one nanomaterial, which will open up a new dimension for the design of combined treatment.