Department of General Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, China.
Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710000, P. R. China.
J Nanobiotechnology. 2024 Jun 14;22(1):334. doi: 10.1186/s12951-024-02551-z.
Due to the limitations of single-model tumor therapeutic strategies, multimodal combination therapy have become a more favorable option to enhance efficacy by compensating for its deficiencies. However, in nanomaterial-based multimodal therapeutics for tumors, exploiting synergistic interactions and cascade relationships of materials to achieve more effective treatments is still a great challenge. Based on this, we constructed a nanoplatform with a "triple-linkage" effect by cleverly integrating polydopamine (PDA), silver nanoparticles (AgNPs), and glucose oxidase (GOx) to realize enhanced photothermal therapy (PTT) and activatable metal ion therapy (MIT) for hepatocellular carcinoma (HCC) treatment. First, the non-radiative conversion of PDA under light conditions was enhanced by AgNPs, which directly enhanced the photothermal conversion efficiency of PDA. In addition, GOx reduced the synthesis of cellular heat shock proteins by interfering with cellular energy metabolism, thereby enhancing cellular sensitivity to PTT. On the other hand, HO, a by-product of GOx-catalyzed glucose, could be used as an activation source to activate non-toxic AgNPs to release cytotoxic Ag, achieving activatable Ag-mediated MIT. In conclusion, this nanosystem achieved efficient PTT and MIT for HCC by exploiting the cascade effect among PDA, AgNPs, and GOx, providing a novel idea for the design of multimodal tumor therapeutic systems with cascade regulation.
由于单模态肿瘤治疗策略的局限性，多模态联合治疗已成为一种更有利的选择，可以通过弥补其不足来提高疗效。然而，在基于纳米材料的肿瘤多模态治疗中，利用材料的协同相互作用和级联关系来实现更有效的治疗仍然是一个巨大的挑战。基于此，我们通过巧妙地整合多巴胺（PDA）、银纳米粒子（AgNPs）和葡萄糖氧化酶（GOx），构建了一个具有“三重连接”效应的纳米平台，以实现增强的光热治疗（PTT）和可激活的金属离子治疗（MIT），用于治疗肝细胞癌（HCC）。首先，AgNPs 增强了 PDA 在光照条件下的非辐射转换，直接提高了 PDA 的光热转换效率。此外，GOx 通过干扰细胞能量代谢来减少细胞热休克蛋白的合成，从而增强细胞对 PTT 的敏感性。另一方面，GOx 催化葡萄糖产生的 H2O2 可以作为激活源，将无毒的 AgNPs 激活为释放细胞毒性 Ag 的 Ag，从而实现可激活的 Ag 介导的 MIT。总之，该纳米系统通过利用 PDA、AgNPs 和 GOx 之间的级联效应，实现了 HCC 的高效 PTT 和 MIT，为具有级联调控的多模态肿瘤治疗系统的设计提供了新的思路。
