As a noninvasive treatment modality, ultrasound (US)triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O 2 ) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H 2 O 2 ) to produce O 2 that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O 2 level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.

Upconversion nanoparticles (UCNPs) and MnO 2 hybrid theranostic nanoplatform (UCMn) is highly desired; however, the rational design of such UCMn hybrid nanomaterials is still a great challenge. Herein, a simple and versatile strategy for the in situ growth of MnO 2 on the surfaces of UCNPs was reported using a sacrificial template method to construct an ideal MnO 2 -disguised and tumor microenvironment−triggered architecture. Such sophisticated architecture not only achieves activatable magnetic resonance imaging and restorable upconversion luminescence (UCL) imaging with over 100-fold enhancement of UCL in vivo but also significantly improves the efficiency of chemodynamic therapy (CDT) by glutathione depletion-and cisplatinactivation-enhanced • OH generation simultaneously. Additionally, the synergetic effect of CDT and chemotherapy presents excellent therapeutic effect in vivo as compared to either CDT or chemotherapy alone. We believe that the ideal design of the MnO 2 -disguised upconversion hybrid nanocomposite will provide more revelations on the future research on nanoscale theranostic systems.

Photodynamic therapy (PDT) of cancers is usually inefficient due to the relatively low level of oxygen in cancer cells; therefore, it needs to combine with other treatment strategies such as chemotherapy or photothermal therapy (PTT) to achieve the best anticancer efficacy. Although porphyrin-containing materials have been widely studied for PDT, the photothermal effect is rarely reported. Herein, nanoscale porphyrin-containing covalent organic polymers (PCOPs) were produced via a room temperature solution-based aging method. The resulting nanoparticles possess high photothermal conversion efficiency (21.7%) and excellent photodynamic effect. For the first time, the in vitro and in vivo tests indicated an enhanced antitumor efficacy for PCOP with combined PDT and PTT. This study provides an efficient approach to fabricate nanoCOP and also demonstrates the great potential of porphyrin-containing COP for biomedical applications.