The effectiveness of a drug may be highly dependent on its delivery to its target organ and even to specific intracellular organelles. In this study we developed nanopartides (NPs) composed of the anionic polypeptide poly-gamma-glutamic acid (gamma-PGA), and a designed amphiphilic and cationic beta-sheet peptide (PFK), which tends to form fibril bilayer assemblies. These peptide assemblies generate hydrophobic niches within the NPs, which enhance the NPs' capacity to deliver amphiphilic drugs. NPs created by coassembly of gamma-PGA and PFK, and further coated with PFK, had a positive zeta-potential and were attracted to mitochondria. When applied to the human osteosarcoma cell line Saos2, the NP-encapsulated lonidamin drug proved to be 300 times more cytotoxic than the free drug.