Coassemblies of the Anionic Polypeptide γ-PGA and Cationic β-Sheet Peptides for Drug Delivery to Mitochondria.
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 nanoparticles (NPs) composed of the anionic polypeptide poly-γ-glutamic acid (γ-PGA), and a designed amphiphilic and cationic β-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 γ-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.
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and Ilse Katz Institute for Nanoscale Science and Technology (IKI), Ben-Gurion University of the Negev , Beer-Sheva 84105, Israel.
Ifat
I
Cohen-Erez
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and Ilse Katz Institute for Nanoscale Science and Technology (IKI), Ben-Gurion University of the Negev , Beer-Sheva 84105, Israel.
Hanna
H
Rapaport
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007191:Indazoles / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010047:Ovalbumin / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D055672:Static Electricity
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007191:Indazoles; D010455:Peptides; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin; C016371:lonidamine