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.