Limited delivery into the nucleus of living cells is a common problem for exogenous matters, e.g. DNA-targeting reagents. A rationally-designed drug carrier could enhance nuclear delivery, however, successful implementation is extremely scarce. Herein, we report a stable and biocompatible Porous-Coordination-Cage (PCC-1) that achieved intranuclear delivery of camptothecin (CPT), a DNA topoisomerase I inhibitor. PCC-1 has a 5.0 nm uniform size, is neutral and hydrophobic, and encapsulates CPT in its cavity. Drug delivery occurred independent of endocytosis and the drug complex was shown to accumulate inside the nucleus of cancer cells. Moreover, the drug complex displays a toxicity towards cultured cancer cells that is superior to free drug, and is capable of inducing a reduction in tumor mass in a xenograft mouse model. Together, these data suggest that PCC-1 is capable of delivering CPT to a nuclear target site and modified PCC structures can serve as highly efficient cell organelle-targeting cargo delivery molecular capsules with high potential in various therapeutic applications.

Cancer nanotherapy promoted by a nuclear targeting molecular capsule

255th National Meeting (2018)

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