Cancer patients suffer from the toxicity of chemotherapy. Antidote, given as a remedy limiting poison, is an effective way to counteract toxicity. However, few antidotes abrogate chemotoxicity without compromising the therapeutic efficacy. Herein, a rationally designed nanoantidote can neutralize chemoagents in normal cells but not enter tumors and thus would not interfere with the efficacy of tumor treatment. The nanoantidote, consisting of a dendrimer core wrapped by reductive cysteine, captures Temozolomide (TMZ, the glioblastoma standard chemotherapy). Meanwhile, thanks to the blood-brain barrier (BBB) and the size of the nanoantidote, the nanoantidote cannot enter glioblastoma. In murine models, the nanoantidote distributes in normal tissues without crossing the BBB, so it markedly reduces the chemotoxicity of TMZ and retains the original TMZ therapeutic efficacy. With most nanotechnologies focusing on antitumor treatment, this detoxicating strategy demonstrates a nanoplatform to reduce chemotoxicity using physiology barriers and introduces a new approach to nanomedicine for cancer chemotherapy.

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