Low tumor-targeting delivery efficiency (Ɛ) and poor tumor penetration remain critical issues in the clinical translation of nanoparticle-based drug delivery systems. Here we report that bienzyme-powered Janus nanorobots with catalase and urease covering the same hemispheres in sequence, demonstrate chemical propulsion far exceeding translational Brownian forces and torques comparable to rotational Brownian torques by leveraging endogenous urea and H₂O₂ gradient in the tumor microenvironment, showcasing ultrasensitive chemotaxis toward biomarkers over-expressed by tumor tissues centimeters away and augmented Ɛ. After intravenous injection into a tumor-bearing mouse model, the nanorobots demonstrate significant enhancement in Ɛ, penetration depth, and cell internalization, surpassing those of passive counterparts by 209, >10, and 1970 times, respectively. When loaded with antitumor drugs, they boost tumor suppression efficacy by ∼49 times compared with passive counterparts. This work offers a new strategy for next-generation drug delivery, promising a paradigm shift for self-propelled nanorobots in precision medicine.
低肿瘤靶向递送效率（Ɛ）与较差的肿瘤渗透性仍然是基于纳米颗粒的药物递送系统临床转化中的关键难题。本研究报道了双酶驱动的Janus纳米机器人，其通过在同一半球依次覆盖过氧化氢酶和脲酶，利用肿瘤微环境中的内源性尿素和H₂O₂梯度，实现了远超平移布朗运动的化学推进力及与旋转布朗扭矩相当的扭矩，展现出对厘米级距离外肿瘤组织过表达生物标志物的超灵敏化学趋向性及增强的Ɛ。在静脉注射至荷瘤小鼠模型后，该纳米机器人表现出显著的Ɛ提升、穿透深度增加及细胞内在化增强，分别达到被动递送系统的209倍、大于10倍和1970倍。当装载抗肿瘤药物时，其肿瘤抑制效果较被动系统提升约49倍。这项工作为下一代药物递送提供了新策略，有望为自驱动纳米机器人在精准医疗领域带来范式转变。
Bienzyme-powered nanorobots with ultrasensitive chemotaxis for precision cancer therapy
肿瘤(癌症)患者之家