Affiliation:
1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry Guangdong Basic Research Center of Excellence for Functional Molecular Engineering School of Chemistry Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital Sun Yat‐Sen University Guangzhou 510006 P. R. China
2. MOE Key Laboratory of Theoretical Organic Chemistry and Functional Molecule School of Chemistry and Chemical Engineering Hunan University of Science and Technology Xiangtan 400201 P. R. China
Abstract
AbstractMultidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non‐apoptosis‐inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt‐Cu1‐4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt‐Cu1 and AFt‐Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt‐Cu2 and AFt‐Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt‐Cu2 and AFt‐Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug‐resistant colon xenograft via intravenous injection. To the best of the authors’ knowledge, this is the first example of metal‐based nucleus‐targeted oncosis inducers overcoming multidrug resistance in vivo.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Natural Science Foundation of Guangdong Province
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials