@misc{liu_selfassembly_of_2019, 
author={Liu, D.,Angelova, A.,Liu, J.,Haramus, V.M.,Angelov, B.,Zhang, X.,Li, Y.,Feger, G.,Li, N.,Zou, A.},
title={Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex},
year={2019},
howpublished = {journal article},
doi = {https://doi.org/10.1039/C9TB00629J},
abstract = {Mitochondria-targeting peptides represent an emergent tool for cancer inhibition. Here supramolecular assemblies of novel amphiphilic cell-penetrating peptides for targeting cancer cell mitochondria are reported. The employed strategy aims at amplifying the apoptotic stimuli by weakening the mitochondrial VDAC1 (voltage-dependent anion channel-1)–hexokinase-II (HK-II) interaction. Peptide engineering is performed with the N-terminus of the HK-II protein, which binds to VDAC1. First, a designed positively charged segment (pKV) is anchored to the specific 15 amino acid sequence (MIASHLLAYFFTELN) to yield a cell-penetrating peptide (pHK-pKV). Second, a lipid chain (Pal) is conjugated to the N-terminus of pHK-pKV in order to enhance the intracellular delivery of the HK-II scaffold. The self-assembly properties of these two synthetic peptides are investigated by synchrotron small-angle X-ray scattering (BioSAXS) and cryogenic transmission electron (cryo-TEM) imaging, which evidence the formation of nanoassemblies of ellipsoid-like shapes. Circular dichroism (CD) spectroscopy demonstrates the induction of partial α-helical structures in the amphiphilic peptides. Confocal microscopy reveals the specific mitochondrial location of Pal-pHK-pKV assemblies in human non-small cell lung cancer (NSCLC) A549 cells. The cytotoxicity and apoptotic studies indicate the enhanced bioactivity of Pal-pHK-pKV self-assembled reservoirs, which cause massive A549 cell death with regard to pHK-pKV. Of significance, Pal-pHK-pKV treatment of non-cancerous NCM460 cells resulted in substantially lower cytotoxicity. The results demonstrate the potential of self-assembled lipo-peptide (HK-II-derived) conjugates as a promising strategy in cancer therapy.},
note = {Online available at: \url{https://doi.org/10.1039/C9TB00629J} (DOI). Liu, D.; Angelova, A.; Liu, J.; Haramus, V.; Angelov, B.; Zhang, X.; Li, Y.; Feger, G.; Li, N.; Zou, A.: Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex. Journal of Materials Chemistry  B. 2019. vol. 7, no. 30, 4706-4716. DOI: 10.1039/C9TB00629J}}