Chemodrug resistance is a major reason accounting for tumor recurrence. Given the mechanistic complexity of chemodrug resistance, molecular inhibitors and targeting drugs often fail to eliminate drug-resistant cancer cells, and sometimes even promote chemoresistance by activating alternative pathways. Here, by exploiting biochemical fragility of high-level but dynamically balanced cellular redox homeostasis in drug-resistant cancer cells, we design a nanosized copper/catechol-based metal–organic framework (CuHPT) that effectively disturbs this homeostasis tilting the balance toward oxidative stress. Within drug-resistant cells, CuHPT starts disassembly that is triggered by persistent consumption of cellular glutathione (GSH). CuHPT disassembly simultaneously releases two structural elements: catechol ligands and reductive copper ions (Cu+). Both of them cooperatively function to amplify the production of intracellular radical oxidative species (ROS) via auto-oxidation and Fenton-like reactions through exhausting GSH. By drastically heightening cellular oxidative stress, CuHPT exhibits selective and potent cytotoxicity to multiple drug-resistant cancer cells. Importantly, CuHPT effectively inhibits in vivo drug-resistant tumor growth and doubles the survival time of tumor-bearing mice. Thus, along with CuHPT’s good biocompatibility, our biochemical, cell biological, preclinical animal model data provide compelling evidence supporting the notion that this copper-based MOF is a predesigned smart therapeutic against drug-resistant cancers through precisely deconstructing their redox homeostasis.

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The therapeutic efficacy of wound infections caused by bacteria is challenged by limited wound repairs and a high risk of inflammation. Microneedles have been generated for wound healing since they are able to efficiently pierce the epidermis and deliver drugs. However, regular microneedles cannot provide oriented traction to “shrink” the wound area, and most microneedles are made of inert polymers, which mainly serve as a support but rarely participate in the following physiological processes. Herein, inspired by lamprey teeth, we designed oriented antibacterial sericin microneedles with dually functionalized needles to provide penetration and directional traction. Sericin, derived from silkworm cocoons, was employed to fabricate microneedle tips, significantly improving skin repair via hair follicle regeneration and angiogenesis. Besides, zinc oxide nanoparticles were integrated as an antibacterial module, endowing the OASM with high bacterial suppression. It is believed that the synergy of these systems may effectively heal infected wounds, suggesting its clinically translational potential.