Catalytic patch activates cancer drug while avoiding side effects

A patch of microneedles carrying palladium nanoparticles can trigger a cancer treatment simply by being pressed onto the skin (Nat. Nanotechnol. 2021, DOI: 10.1038/s41565-021-00910-7). Transforming a benign prodrug into an active medicine at a particular site in the body offers a way to deliver concentrated doses while avoiding systemic side effects. Researchers already use variousreactions to activate prodrugs, but those that require transition-metal catalysts raise toxicity concerns. “This has limited the clinical translation of such methods,” says Zhen Gu of Zhejiang University. So Gu’s team created an array of polyvinyl alcohol microneedles that contain titania nanosheets bearing catalytic palladium nanoparticles. The needles are strong enough to pierce skin, but inside the body they become porous, providing access to the catalyst without leaching any metal. The researchers modified the cancer drug doxorubicin with an allyloxycarbonyl group, reducing the drug’s toxicity by a factor of 120. After scientists applied the patch to mice with melanoma tumors and injected the prodrug, palladium particles removed the allyloxycarbonyl groups, converting the prodrug to doxorubicin. This strategy caused few side effects and slowed tumor growth. After 2 weeks, tumors treated with doxorubicin alone were three times as large as those treated with the patch and prodrug. The patch was easily removed, with no skin damage or loss of palladium.