Microwave-Actuated "Nano-Rocket" with Janus Structure for Spatiotemporal Drugs Release to Enhance Anticancer Efficacy

Multi-drug combination therapy can compensate for the deficiency of a single drug and enhance the therapeutic effect of chemotherapy. However, due to a single drug release strategy and limitations in cellular drug uptake caused by dense connective tissue, cell membrane barrier, etc., the multi-drug nanoplatforms often fall short of on-demand drug delivery. To address these, a nano-rocket (DDS-ZPDMP) is designed to achieve intracellular enrichment and spatiotemporal drug release for tumor treatment. The microwave (MW)-actuated nano-rocket consists of cobalt-based metal-organic frameworks (ZIF-67) as the "rocket booster" and silica with dendritic apertures (DMSNs) as the "rocket payload". It realizes autonomous movement by the oxygen production performance of ZIF-67 and the Janus structure. In the push of the "rocket booster", more DDS-ZPDMP is ingested by the tumor cell, which can achieve tumor treatment in an order- and location-dependent drug released. In the tumor microenvironment (TME), the degradation difference between DMSNs and ZIF-67 in DDS-ZPDMP makes sequential drug release come true. The 6-Diazo-5-oxo-L-norleucine (DON) loaded outside is released to disrupt the TME at first, and then DMSNs carrying doxorubicin (DOX) are enriched in tumor cells and constantly released, thereby improving the therapeutic effect of chemotherapy drugs. The nano-rocket provides an effective treatment of tumors by spatiotemporally delivering drugs.