Intravesical instillation is the common therapeutic strategy for bladder cancer. Besides chemo drugs, nanoparticles are used as intravesical instillation reagents, offering appealing therapeutic approaches for bladder cancer treatment. Metal oxide nanoparticle based chemodynamic therapy (CDT) converts tumor intracellular hydrogen peroxide to ROS with cancer cell-specific toxicity, which makes it a promising approach for the intravesical instillation of bladder cancer. However, the limited penetration of nanoparticle based therapeutic agents into the mucosa layer of the bladder wall poses a great challenge for the clinical application of CDT in intravesical instillation. Herein, we developed a 1064 nm NIR-II light driven hydrogel nanomotor for the CDT for bladder cancer via intravesical instillation. The hydrogel nanomotor was synthesized via microfluidics, wrapped with a lipid bilayer, and encapsulates CuO₂ nanoparticles as a CDT reagent and core–shell structured Fe₃O₄@Cu₉S₈ nanoparticles as a fuel reagent with asymmetric distribution in the nanomotor (LipGel-NM). An NIR-II light irradiation of 1064 nm drives the active motion of LipGel-NMs, thus facilitating their distribution in the bladder and deep penetration into the mucosa layer of the bladder wall. After FA-mediated endocytosis in bladder cancer cells, CuO₂ is released from LipGel-NMs due to the acidic intracellular environment for CDT. The NIR-II light powered active motion of LipGel-NMs effectively enhances CDT, providing a promising strategy for bladder cancer therapy.

中文翻译：

---

NIR-II 光动力水凝胶纳米马达用于膀胱内灌注，增强膀胱癌治疗

膀胱内灌注是膀胱癌的常见治疗策略。除了化疗药物外，纳米颗粒还用作膀胱内滴注试剂，为膀胱癌的治疗提供了有吸引力的治疗方法。基于金属氧化物纳米颗粒的化学动力学疗法（CDT）将肿瘤细胞内的过氧化氢转化为具有癌细胞特异性毒性的ROS，这使其成为膀胱癌膀胱内灌注的一种有前景的方法。然而，基于纳米颗粒的治疗剂对膀胱壁粘膜层的渗透有限，这给CDT膀胱灌注的临床应用带来了巨大的挑战。在此，我们开发了一种 1064 nm NIR-II 光驱动的水凝胶纳米马达，用于通过膀胱内滴注对膀胱癌进行 CDT 。水凝胶纳米马达是通过微流体合成的，包裹着脂质双层，并封装CuO ₂纳米粒子作为CDT试剂和核壳结构的Fe ₃ O ₄ @Cu ₉ S ₈纳米粒子作为燃料试剂，在纳米马达中不对称分布（LipGel -近乎纳米）。 1064 nm 的 NIR-II 光照射驱动 LipGel-NM 的主动运动，从而促进其在膀胱中的分布并深入渗透到膀胱壁的粘膜层。在膀胱癌细胞中，FA介导的内吞作用后，由于CDT的酸性细胞内环境， CuO ₂从LipGel-NMs中释放出来。 LipGel-NM 的 NIR-II 光驱动主动运动有效增强 CDT，为膀胱癌治疗提供了一种有前景的策略。