A simple self-assembling system of melittin for hepatoma treatment

Abstract

Background Hepatoma is a serious public health concern. New attempts are urgently needed to solve this problem. Melittin, a host defense peptide derived from the venom of honeybees, has noteworthy hemolysis and non-specific cytotoxicity in clinical applications. Here, the self-assembly of melittin and vitamin E-succinic acid-(glutamate)12 (VG) was fabricated via noncovalent π-stacking and hydrogen bonding interactions using an environment-friendly method without “toxic” solvents. Results As expected, the designed self-assembly (denoted as M/VG nanoparticles) exhibits a uniform morphology with a particle size of approximately 60 nm and a zeta potential of approximately − 26.8 mV. Furthermore, added VG significantly decreased hemolytic activity, increased tumor-targeted effects, and accelerated apoptosis. Conclusion Our research provides a promising strategy for the development of natural self-assembled biological peptides for clinical application, particularly for transforming toxic peptides into safe therapeutic systems. Graphical Abstract

Mini-αA-Crystallin Stifled Melittin-Induced Haemolysis and Lymphocyte Lysis

“…Melittin is a small cell membrane lytic peptide (26 amino acids, 2.846 KDa, and 2 α-helical segments) that can damage membrane phospholipids, including those found in erythrocytes and lymphocytes, causing haemolysis and lymphocyte lysis ( Van et al 2008;Gajski and Garaj-Vrhovac 2013;Kim 2021;Jin et al 2023). Under physiological conditions, it has been demonstrated that melittin exists as a random coil, but when it comes in contact with the cell membrane, it forms a monomeric α-helix and interacts with the membrane, leading to membrane lysis (Buck 1998;Goto and Hagihara 1992;Raghuraman and Chattopadhyay 2007;Saini et al 1999).…”

“…However, many researchers have probed the therapeutic potential of melittin and found it to be effective as an anti-cancer (Gajski and Garaj 2013), antiviral (Memariani et al 2020), and anti-microbial (Asthana et al 2004;Hanulova et al 2009) agent. The use of melittin has been restricted due to its side effects, particularly its haemolysis (DeGrado et al 1982;Tender et al 2021;Jin et al 2023).…”