Recently, ultrasmall gadolinium oxide (Gd₂O₃) nanoparticles with high longitudinal relaxation rate have received enormous attention. However, it can't be concentrated in tumor site through intravenous administration due to its ultrasmall size. In this project, we coated ultrasmall Gd₂O₃ nanoparticles with a near-infrared (NIR) light-absorbing polymer polypyrrole (PPy), modifying with hyaluronic acid (HA) and loaded aluminum phthalocyanine (AlPc), the Gd₂O₃@PPy/AlPc-HA nanoparticles could be used for fluorescence (FL)/magnetic resonance (MR)/photoacoustic (PA) imaging guided as well as remotely controlled PTT/PDT combined anti-tumor therapy. Polymerized PPy with high photothermal conversion efficiency was introduced to assemble the ultrasmall Gd₂O₃ nanoparticles which have high longitudinal relaxation rate and signal-to-noise ratio, thus obtaining Gd₂O₃@PPy nanoparticles which possess a larger particle size and can be more suitable for tumor targeting based on the EPR effect. HA and AlPc were adsorbed on PPy for HA-mediated tumor targeting and photodynamic therapy respectively. The in vivo triple-modal imaging revealed that Gd₂O₃@PPy/AlPc-HA nanoparticles possess enhanced tumor uptake effect after intravenous injection. More importantly, the nanoparticles exhibited an obvious photothermal effect, which can trigger the release and de-quench of AlPc. The anti-tumor efficiency further corroborated that the combined therapy achieved an excellent tumor inhibition therapeutic effect which was much better than any other mono-therapy. Consequently, our work encouraged further exploration of polymer-based multifunctional theranostic nanoparticles for cancer combination therapy under remote near-infrared (NIR) light controls.

近来，具有高纵向弛豫率的超小氧化oxide（Gd ₂ O ₃）纳米颗粒受到了极大的关注。然而，由于其超小尺寸，它不能通过静脉内给药集中在肿瘤部位。在该项目中，我们用近红外（NIR）吸光聚合物聚吡咯（PPy）涂覆了超小Gd ₂ O ₃纳米颗粒，并用透明质酸（HA）和负载的酞菁铝（AlPc）进行了修饰，添加了Gd ₂ O ₃@ PPy / AlPc-HA纳米粒子可用于指导的荧光（FL）/磁共振（MR）/光声（PA）成像以及远程控制的PTT / PDT联合抗肿瘤治疗。引入具有高光热转化效率的聚合PPy来组装具有高纵向弛豫率和信噪比的超小Gd ₂ O ₃纳米颗粒，从而获得具有较大粒径且可以被制备的Gd ₂ O ₃ @PPy纳米颗粒。基于EPR效果更适合肿瘤靶向。HA和AlPc分别吸附在PPy上，用于HA介导的肿瘤靶向和光动力疗法。体内三峰成像显示Gd ₂ O ₃静脉注射后，@ PPy / AlPc-HA纳米颗粒具有增强的肿瘤吸收作用。更重要的是，纳米颗粒表现出明显的光热效应，可以触发AlPc的释放和去猝灭。抗肿瘤效率进一步证实了联合疗法取得了优异的抑瘤治疗效果，远优于其他任何单一疗法。因此，我们的工作鼓励在基于远距离近红外（NIR）光控制的癌症组合疗法中进一步探索基于聚合物的多功能治疗治疗纳米颗粒。