467549 Posh Inhibitor Peptide Amphiphile Micelles As a Novel Leukemia Therapeutic Modality
POSH peptide amphiphiles were synthesized by covalently conjugating two hydrophobic aliphatic palmitic acid tails to POSH peptides which were found to self-assembly into small and mostly spherical micelles in water at very low concentrations. Since ALL is a blood-borne cancer, therapeutics need to be capable of being delivered intravenously so small, spherical micelles are an ideal device. Interestingly, spherical micellization often requires the use of an additional hydrophilic linker (e.g. PEG) to achieve the desirable micelle shape, but the highly hydrophilic and charged nature of the POSH peptide facilitated spherical micelle formation without additional components. Confocal microscopy revealed that fluorescently-labeled POSH PAMs are readily uptaken by even non-phagocytic cells indicating their intracellular payload potential. To determine the enhanced cancer cytotoxicity of POSH PAMs they were incubated with three different leukemic cell lines (murine LM-138, human Mec-1, and human Mec-2) and their effects were compared to the known cytotoxic peptide TAT-POSH. POSH PAMs was found to greatly outperform TAT-POSH inducing enhanced cytotoxicity at every dose and similar cytotoxicity at a sixteenth to an eighth of the dose. The capacity for POSH PAMs to improve cancer cytotoxicity over a gold-standard cell penetrating peptide like TAT is a quite exciting discovery. These results provide strong evidence that POSH PAMs hold tremendous promise as an ALL treatment modality.
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