| May 08, 2026 |
A two-step nanoparticle system first blocks cancer cells’ drug-expulsion mechanism, then releases chemotherapy combined with laser-driven heat to destroy resistant tumors.
(Nanowerk News) 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.
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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.
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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 Cécilia Ménard-Moyon at the French National Centre for Scientific Research (CNRS)/University of Strasbourg.
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The findings were published in Journal of Controlled Release (“Multifunctional amino acid-based nanoparticles for sequential drug delivery to overcome multidrug resistant cancer”).
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| Concept of this study. (Image: Reproduced from DOI:10.1016/j.jconrel.2026.114954, CC BY) (click on image to enlarge)
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Multidrug resistance (MDR) is one of the most formidable obstacles in cancer chemotherapy. MDR cancer cells overexpress P-glycoprotein (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.
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“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,” explains Miyako. “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.”
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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.
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The results of in vitro experiments on cells far exceed the efficacy of either chemotherapy or photothermal therapy alone. Similarly, tumor-bearing mice undergoing this three-pronged treatment showed complete tumor regression compared to photothermal alone, which showed only transient regression followed by recurrence.
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Multidrug resistance affects a wide range of cancers and remains a largely unsolved clinical challenge. This platform offers a new and potentially broadly applicable strategy to restore chemotherapy sensitivity in tumors that have stopped responding to treatment.
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“We are hopeful that this approach could become a beacon of hope for patients with cancer one day,” says Miyako. “The nanoparticles are constructed entirely from amino acid-derived building blocks and biocompatible materials, which underscores the potential for clinical translatability in humans.”
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