组合疗法是克服肝细胞癌（HCC）化疗中多药耐药（MDR）的新兴策略。然而，传统的输送系统中的被动扩散显著阻碍药物进入肝细胞癌细胞的途径与渗透，从而阻碍组合疗法的疗效。微/纳米马达作为一种在微小尺度上可自主运动的载药平台，为解决这个问题提供了可能性。在此，作者展示了一种活性药物输送微马达平台，精心设计以装载具有不同物理化学性质的药物，并增强细胞药物渗透性，以用于HCC化疗治疗。生物相容性微马达平台Mg/PLGA/CHI由镁（Mg）为核心，包裹两层聚乳酸-羟基乙酸共聚物（PLGA）和壳聚糖（CHI）制成。其中，疏水性药物多柔比星（Dox）和亚硝基丁二酮（Cur）分别被加载。微马达的自主运动速度高达45 μm/s，大大增强了化疗药物的扩散，并导致更高的细胞外和细胞内药物分布。此外，行动过程中产生的氢气可消除人体肝细胞癌（HepG2）细胞中过量的活性氧（ROS）。与惰性微马达组相比，活性微马达中Dox和Cur的吸收量在人体肝细胞癌细胞中分别高出约2.9倍和1.5倍。此外，在微马达浓度为1 mg/mL时，抗肿瘤活性也明显提高（细胞增殖减少约30%）。总体而言，本研究提出了一种基于活性输送系统上载不同化疗药物的方法，以增强药物渗透性并克服MDR，并为HCC治疗提供了潜在有效的治疗策略。

Combination therapy is an emerging strategy to overcome multidrug resistance (MDR) in hepatocellular carcinoma (HCC) chemotherapy treatment. However, the passive diffusion in traditional delivery systems greatly retards the approach and penetration of drugs into hepatocellular carcinoma cells and thus hinders the efficacy of combination therapy. Micro/nanomotors with autonomous locomotion in a tiny scale provide the possibility of tackling this issue. Herein, an active drug delivery micromotor platform delicately designed to load drugs with different physicochemical properties and enhance the drug permeability of cells is demonstrated for HCC chemotherapy treatment. The biocompatible micromotor platform Mg/PLGA/CHI comprised magnesium (Mg) coated with two polymer layers made of poly(lactic-co-glycolic acid) (PLGA) and chitosan (CHI), where the hydrophobic and hydrophilic drugs doxorubicin (Dox) and Curcumin (Cur) were loaded, respectively. The autonomous motion of the micromotors with velocity up to 45 μm s-1 greatly enhanced the diffusion of chemotherapeutic drugs and led to higher extracellular and intracellular drug distribution. Moreover, hydrogen produced during the motion eliminated the excess reactive oxygen species (ROS) in the human hepatocellular carcinoma (HepG2) cells. Compared with inert groups, the absorption of Dox and Cur from the active micromotors was about 2.9 and 1.5 times higher in human hepatocellular carcinoma (HepG2) cells. In addition, the anti-tumor activity also obviously improved at the micromotor concentration of 1 mg mL-1 (cell proliferation was reduced by almost 30%). Overall, this work proposes an approach based on loading different chemotherapy agents on an active delivery system to enhance drug permeability and overcome MDR and provides a potentially effective therapeutic strategy for the treatment of HCC.