A stable biocompatible porous coordination cage promotes in vivo liver tumor inhibition

Many emerging strategies in chemo-, gene-, and immunotherapy require the accumulation of reagents in the cell nucleus. However, their delivery into the nucleus is often limited. Nuclear delivery could be enhanced with a rationally designed cargo-delivery scaffold, but this approach has rarely been successfully implemented. Herein, a stable, biocompatible molecular capsule that encapsulates and delivers camptothecin, a DNA topoisomerase I inhibitor, into the nucleus of living cells was reported. Nuclear delivery is facilitated by the ultra-small diameter, zero net charge, and hydrophobicity of the capsule. The encapsulated drug complex displays superior toxicity towards multiple cancer cells over the free drug, the Food and Drug Administration (FDA) approved drugs, as well as conventionally reported drug vectors. Additionally, it inhibits liver cancer tumor growth in a xenograft mouse model. Modification of the properties of such molecular capsules may make it possible to design therapeutic strategies that target specific cell organelles.