A drug co-delivery platform made of magnesium-based micromotors enhances combination therapy for hepatoma carcinoma cells

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 mu m 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. An active drug delivery platform of Mg micromotors is proposed to overcome MDR and enhance drug permeability for treating HCC.

Automated summary

An active drug delivery platform of Mg micromotors is proposed to overcome MDR and enhance drug permeability for treating HCC. The platform, made of biocompatible materials, allows autonomous motion and increases the diffusion of chemotherapy drugs, leading to improved drug distribution within cells. Moreover, the hydrogen produced during the motion helps eliminate reactive oxygen species in cells. Compared to inert groups, the absorption of drugs from the active micromotors is significantly higher. At a concentration of 1 mg/mL, the micromotors also exhibit enhanced anti-tumor activity, reducing cell proliferation by almost 30%.