Spatio-temporal Self-Assembly Determines Cancer Selective Toxcity
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- Spatio-temporal Self-Assembly Determines Cancer Selective Toxcity
- Jin, Sung eon; Lee, Eunji; Ryu, Ja-Hyoung
- Issue Date
- Korean Chemical Society
- 125th General Meeting of the Korean Chemical Society
- Intracellular or pericellular self-assembly of amphiphilic peptides are emerging as a potent cancer therapeutic strategy. Achieving self-assembly of amphiphilic peptides inside of a cell or cellular organelle is challenging due to the complex cellular environment consisting several hydrophobic and hydrophilic biomolecules that may alter the self-assembling propensity of the amphiphilic peptides. Hence, among the different electrostatic forces, the hydrophobic-hydrophilic balance between the building units plays a major role in determining the self-assembling propensity of amphiphilic peptides within the cell. Herein, we show the impact of hydrophobic–hydrophilic balance between the building units of the amphiphilic peptides in controlling the cellular fate during their self-assembly inside the mitochondria. A series of peptides were designed to target and self-assembles inside the mitochondria of the cancer cells. Hydrophobicity of the peptides were tuned by varying the N-terminus capping of the peptides. Analysis showed that highest hydrophobic peptide self-assembles before reaching the mitochondria and showed no selectivity towards cancer cells, while hydrophilic peptides could not self-assemble inside the mitochondria. Optimum balance between hydrophobicity-hydrophilicity is critical factor to achieve self-assembly inside the mitochondria and thereby providing higher selectivity towards cancer cells
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