Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H 2 O 2 into hydroxyl radical (•OH), but endogenous H 2 O 2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H 2 O 2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H 2 O 2 . The CP nanodots were prepared through coordination of H 2 O 2 to Cu 2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu 2+ and H 2 O 2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.

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Weyl semimetals provide the realization of Weyl fermions in solid-state physics. Among all the physical phenomena that are enabled by Weyl semimetals, the chiral anomaly is the most unusual one. Here, we report signatures of the chiral anomaly in the magneto-transport measurements on the first Weyl semimetal TaAs. We show negative magnetoresistance under parallel electric and magnetic fields, that is, unlike most metals whose resistivity increases under an external magnetic field, we observe that our high mobility TaAs samples become more conductive as a magnetic field is applied along the direction of the current for certain ranges of the field strength. We present systematically detailed data and careful analyses, which allow us to exclude other possible origins of the observed negative magnetoresistance. Our transport data, corroborated by photoemission measurements, first-principles calculations and theoretical analyses, collectively demonstrate signatures of the Weyl fermion chiral anomaly in the magneto-transport of TaAs.

The movement of anionic porphyrins (for example, haem) across intracellular membranes is crucial to many biological processes, but their mitochondrial translocation and coordination with haem biosynthesis is not understood. Transport of porphyrins into isolated mitochondria is energy-dependent, as expected for the movement of anions into a negatively charged environment. ATP-binding cassette transporters actively facilitate the transmembrane movement of substances. We found that the mitochondrial ATP-binding cassette transporter ABCB6 is upregulated (messenger RNA and protein in human and mouse cells) by elevation of cellular porphyrins and postulated that ABCB6 has a function in porphyrin transport. We also predicted that ABCB6 is functionally linked to haem biosynthesis, because its mRNA is found in both human bone marrow and CD71+ early erythroid cells (by database searching), and because our results show that ABCB6 is highly expressed in human fetal liver, and Abcb6 in mouse embryonic liver. Here we demonstrate that ABCB6 is uniquely located in the outer mitochondrial membrane and is required for mitochondrial porphyrin uptake. After ABCB6 is upregulated in response to increased intracellular porphyrin, mitochondrial porphyrin uptake activates de novo porphyrin biosynthesis. This process is blocked when the Abcb6 gene is silenced. Our results challenge previous assumptions about the intracellular movement of porphyrins and the factors controlling haem biosynthesis.