Cardiotoxicity, particularly that linked to the hERG channel, remains one of the biggest obstacles in the development of new drugs. This type of toxicity, responsible for the withdrawal of many promising molecules, slows down the market launch of effective treatments. To address this issue, an international team involving three CNRS laboratories has developed an innovative approach: encapsulating drugs in nanosystems capable of limiting this toxicity while enhancing their action.

Based on self-assembled amphiphilic dendrimers, this nanoplatform exploits the tree-like structure and versatility of these molecules to create uniform nanomicelles capable of efficiently transporting and releasing various therapeutic compounds. Researchers at CINaM, CRCM (Nelson Dusetti, Juan Iovanna) and CRMBM tested this strategy on three molecules well known for their binding to the hERG channel: chloroquine, doxorubicin and ZZW115, an emerging anti-cancer compound.

The results are impressive: the encapsulated molecules showed significantly reduced affinity for the hERG channel, thereby reducing cardiac risk, while maintaining or even improving their efficacy. In vivo imaging also confirmed better distribution of treatments in target tissues, whether in the liver for chloroquine or in tumours in the case of cancer treatments.

This work opens up promising avenues for reviving drugs that had been abandoned due to cardiotoxicity and accelerating the development of new, safer therapies. It represents a breakthrough at the intersection of nanotechnology and pharmacology, redefining the way treatments are designed and administered.

Liu X, Dhumal D, Santofimia-Castaño P, Liu J, Casanova M, Garcia-Muñoz AC, Perles-Barbacaru TA, Elkihel A, Zhang W, Roussel T, Galanakou C, Wu J, Zerva E, Dusetti N, Xia Y, Liang XJ, Viola A, Iovanna JL, Peng L. Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy. Sci Adv. 2025 Jun 27;11(26):eadu9948.

More information on the CNRS website.