696
Views
17
Crossref
17
WoS
13
Scopus
1
CSCD
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.
We gratefully acknowledge the National Natural Science Foundation of China (No. 22071049). We also thank the fund from China Hunan Provincial Science & Technology Department (No. 2020RC3020). We would like to thank Dr. Yanyan Huang Ms. Yuanyuan Zhu and Dr. Rui Zhao from Institute of Chemistry, Chinese Academy of Sciences for their kind guidance and support in the animal tests. We also deeply appreciate Dr. Xizhen Lian and Dr. Jean-Philippe Pellois from Department of Biochemistry and Biophysics, Texas A & M University for their contributions for cell experiments and manuscript discussions. We also want to thank Dr. Guo Fu and Dr. Beiyan Nan from Department of Biology, Texas A & M University for their help in fluorescence microscopy. We would like to show gratitude to Dr. Feng Zhang from Division of Pharmaceutics, The University of Texas at Austin for his kind support in pharmacology. The animal study protocol was approved by the Institutional Animal Care and Use Committee at Hunan University.