Nanomaterial-Based Organelles Protect Normal Cells against Chemotherapy-Induced Cytotoxicity

Abstract

Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus. Cells with implanted Au-ODN are more robust since their viability is maintained during DOX treatment. In vivo experiments confirm that the Au-ODN nanomaterials selectively concentrate in hepatocytes and eliminate DOX-induced hepatotoxicity, increasing the cell's capacity to resist the threatening chemotherapeutic milieu. The finding suggests that introducing functional materials as biological devices into living systems may be a new strategy for improving the regulation of cell fate in more complex conditions and for manufacturing super cells.

Keywords: artificial organelles; chemotherapy; cytotoxicity; nanomaterials; normal cells.