Cancer cells frequently develop the ability to expel anticancer drugs before they can work — a phenomenon called multidrug resistance (MDR) — which is one of the leading reasons why chemotherapy fails in patients. This research addresses that problem with a fundamentally new strategy: instead of simply increasing drug doses or switching drugs, researchers engineered nanoparticles that first disable the cancer cell’s drug-expulsion mechanism, and only then release the anticancer drug. By combining this sequential drug delivery approach with photothermal therapy (using near-infrared laser light to heat and destroy the tumor), complete tumor elimination and 100% survival in a mouse model of drug-resistant cancer was achieved, with no detectable toxicity to normal tissues.<\/p>\n
This remarkable drug delivery system was developed by an international research team led by Professor Eijiro Miyako at Tohoku University, who is also a Visiting Professor at Japan Advanced Institute of Science and Technology, in collaboration with the group of Drs. Alberto Bianco and C\u00e9cilia M\u00e9nard-Moyon at the French National Centre for Scientific Research (CNRS)\/University of Strasbourg. The findings were published in the prestigious Journal of Controlled Release on May 6, 2026.<\/p>\n
Multidrug resistance (MDR) is one of the most formidable obstacles in cancer chemotherapy. MDR cancer cells overexpress P-glycoprotein<\/a> (P-gp), a drug efflux pump that actively expels chemotherapeutic agents before they can exert their therapeutic effect, drastically reducing intracellular drug concentrations. Previous studies have looked at a combined, simultaneous release of P-gp inhibitors with anticancer drugs as a treatment for MDR cancer, but showed limited efficacy.<\/p>\n
<\/p>\n We wanted to first inhibit the expelling action of P-gp before anticancer drugs are introduced, so we developed a unique, sequential release mechanism to achieve this. Afterall, you need to patch up a hole in a leaky bucket before adding more water, instead of trying to do both at the same time.”<\/p>\n
\u00a0Professor Eijiro Miyako at Tohoku University<\/p>\n
<\/p>\n The controlled, timed release allows for more targeted care. The research team developed porous amino acid nanoparticles (NPs) that were able to contain the anticancer drug doxorubicin (Dox), and the P-gp inhibitor quinidine. The NPs integrate three therapeutic functions: sequential drug release, photothermal therapy, and active tumor targeting.<\/p>\n
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