Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides
Here we present the development of nanoparticles (NPs) formulations specifically designed for targeting the antiapoptotic Bcl-2 proteins on the outer membrane of mitochondria with the drug agent ABT-737. The NPs which are self-assembled by the natural polypeptide poly gamma glutamic acid (ϒPGA) and...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2024-02-01
|
Series: | Heliyon |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024021261 |
_version_ | 1797267743664242688 |
---|---|
author | Polina Aibinder Ifat Cohen-Erez Hanna Rapaport |
author_facet | Polina Aibinder Ifat Cohen-Erez Hanna Rapaport |
author_sort | Polina Aibinder |
collection | DOAJ |
description | Here we present the development of nanoparticles (NPs) formulations specifically designed for targeting the antiapoptotic Bcl-2 proteins on the outer membrane of mitochondria with the drug agent ABT-737. The NPs which are self-assembled by the natural polypeptide poly gamma glutamic acid (ϒPGA) and a designed cationic and amphiphilic peptide (PFK) have been shown to target drugs toward mitochondria. In this study we systematically developed the formulation of such NPs loaded with the ABT-737 and demonstrated the cytotoxic effect of the best identified formulation on MDA-MB-231 cells. Our findings emphasize the critical role of solutions pH and the charged state of the components throughout the formulation process as well as the concentrations of the co-components and their mixing sequence, in achieving the most stable and effective cytotoxic formulation. Our study highlights the potential versatility of designed peptides in combination with biopolymers for improving drug delivery formulations and enhance their targeting abilities. |
first_indexed | 2024-03-07T22:54:21Z |
format | Article |
id | doaj.art-799195bd891e43f9bf178cea7a01755f |
institution | Directory Open Access Journal |
issn | 2405-8440 |
language | English |
last_indexed | 2024-04-25T01:21:26Z |
publishDate | 2024-02-01 |
publisher | Elsevier |
record_format | Article |
series | Heliyon |
spelling | doaj.art-799195bd891e43f9bf178cea7a01755f2024-03-09T09:27:12ZengElsevierHeliyon2405-84402024-02-01104e26095Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptidesPolina Aibinder0Ifat Cohen-Erez1Hanna Rapaport2Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, IsraelAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; Ilse Katz Institute for Nanoscale Science and Technology (IKI), Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; Corresponding author. Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.Here we present the development of nanoparticles (NPs) formulations specifically designed for targeting the antiapoptotic Bcl-2 proteins on the outer membrane of mitochondria with the drug agent ABT-737. The NPs which are self-assembled by the natural polypeptide poly gamma glutamic acid (ϒPGA) and a designed cationic and amphiphilic peptide (PFK) have been shown to target drugs toward mitochondria. In this study we systematically developed the formulation of such NPs loaded with the ABT-737 and demonstrated the cytotoxic effect of the best identified formulation on MDA-MB-231 cells. Our findings emphasize the critical role of solutions pH and the charged state of the components throughout the formulation process as well as the concentrations of the co-components and their mixing sequence, in achieving the most stable and effective cytotoxic formulation. Our study highlights the potential versatility of designed peptides in combination with biopolymers for improving drug delivery formulations and enhance their targeting abilities.http://www.sciencedirect.com/science/article/pii/S2405844024021261ApoptosisBCL-2β-sheet peptidesSelf-assemblyDrug deliveryCytotoxicity |
spellingShingle | Polina Aibinder Ifat Cohen-Erez Hanna Rapaport Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides Heliyon Apoptosis BCL-2 β-sheet peptides Self-assembly Drug delivery Cytotoxicity |
title | Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides |
title_full | Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides |
title_fullStr | Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides |
title_full_unstemmed | Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides |
title_short | Rational Formulation of targeted ABT-737 nanoparticles by self-assembled polypeptides and designed peptides |
title_sort | rational formulation of targeted abt 737 nanoparticles by self assembled polypeptides and designed peptides |
topic | Apoptosis BCL-2 β-sheet peptides Self-assembly Drug delivery Cytotoxicity |
url | http://www.sciencedirect.com/science/article/pii/S2405844024021261 |
work_keys_str_mv | AT polinaaibinder rationalformulationoftargetedabt737nanoparticlesbyselfassembledpolypeptidesanddesignedpeptides AT ifatcohenerez rationalformulationoftargetedabt737nanoparticlesbyselfassembledpolypeptidesanddesignedpeptides AT hannarapaport rationalformulationoftargetedabt737nanoparticlesbyselfassembledpolypeptidesanddesignedpeptides |