Double-Layered Metal-Organic-Frameworks-Based Microswimmers for Adaptive Dual-Drug Anti-Cancer Therapy Using Artemisinin-Based Compounds

Magnetic microrobots have the potential for anti-cancer drug delivery; however, using dual-drug to counter drug resistance, a critical issue in cancer research, has only been briefly investigated. This study introduces the double-layered metal-organic-frameworks (MOFs)-based microswimmers for sustained dual-drug delivery. These microswimmers are made up of ZIF-8 and MIL-100, biocompatible MOFs, that can selectively adsorb two types of drugs. The MOFs increase the surface area of the microswimmers by ≈2.42 times, which greatly enhances drug adsorption, and improves hydrophilicity, which reduces adhesion for surface locomotion. Their biocompatibility and dual-drug adsorption are verified through cell viability and drug-loading tests. The microswimmers have remarkable versatility in loading different drug combinations (DHA + 5-FU, CPT-11, or DOX), indicating the potential for adaptive therapy. They can inhibit cancer cells for up to 72 h through the sustained release of dual drugs. In contrast, drug treatments without microswimmers only inhibit cell proliferation for 24 h, leading to a significant rebound. This study provides a method to mass fabricate fully biocompatible microrobots with dual drug loading versatility and high drug adsorption capacity; thus, suggests a powerful platform for sustained adaptive dual-drug therapy.