TY - JOUR
T1 - Reproducible and Characterized Method for Ponatinib Encapsulation into Biomimetic Lipid Nanoparticles as a Platform for Multi-Tyrosine Kinase-Targeted Therapy
T2 - ACS Applied Bio Materials
AU - Zinger, Assaf
AU - Baudo, Gherardo
AU - Naoi, Tomoyuki
AU - Giordano, Federica
AU - Lenna, Stefania
AU - Massaro, Matteo
AU - Ewing, April
AU - Kim, Ha Ram
AU - Tasciotti, Ennio
AU - Yustein, Jason T.
AU - Taraballi, Francesca
N1 - Funding Information:
Research reported in this publication was supported by the Cancer Prevention and Research Institute of Texas (CPRIT- RP180394) and the Hearst Kleberg foundations and BSP Pharmaceuticals, Latina, Italy. The various nanoparticles solutions were vitrified and imaged by Mr. Isaac Forrester at the Baylor College of Medicine Cryo-Electron Microsocopy Core Facility (BCM, Houston, TX). The authors want also to acknowledge Dr. Enrica De Rosa, Ms. Manuela Sushnitha, and Ms. Tamara Zinger for their help in preparing this work for publication. was created using Biorender.com
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/10/19
Y1 - 2020/10/19
N2 - Ponatinib (Pon) is a multi-tyrosine kinase inhibitor that demonstrated high efficiency for treating cancer. However, severe side effects caused by Pon off-targeting effects prevent its extensive use. Using our understanding into the mechanisms by which Pon is transported by bovine serum albumin in the blood, we have successfully encapsulated Pon into a biomimetic nanoparticle (NP). This lipid NP (i.e., "leukosomes") incorporates membrane proteins purified from activated leukocytes that enable immune evasion, and enhanced targeting of inflamed endothelium NPs have been characterized for their size, charge, and encapsulation efficiency. Membrane proteins enriched on the NP surface enabled modulation of Pon release. These NP formulations showed promising dose-response results on two different murine osteosarcoma cell lines, F420 and RF379. Our results indicate that our fabrication method is reproducible, nonuser-dependent, efficient in loading Pon, and applicable toward repurposing numerous therapeutic agents previously shelved due to toxicity profiles.
AB - Ponatinib (Pon) is a multi-tyrosine kinase inhibitor that demonstrated high efficiency for treating cancer. However, severe side effects caused by Pon off-targeting effects prevent its extensive use. Using our understanding into the mechanisms by which Pon is transported by bovine serum albumin in the blood, we have successfully encapsulated Pon into a biomimetic nanoparticle (NP). This lipid NP (i.e., "leukosomes") incorporates membrane proteins purified from activated leukocytes that enable immune evasion, and enhanced targeting of inflamed endothelium NPs have been characterized for their size, charge, and encapsulation efficiency. Membrane proteins enriched on the NP surface enabled modulation of Pon release. These NP formulations showed promising dose-response results on two different murine osteosarcoma cell lines, F420 and RF379. Our results indicate that our fabrication method is reproducible, nonuser-dependent, efficient in loading Pon, and applicable toward repurposing numerous therapeutic agents previously shelved due to toxicity profiles.
KW - biomimicry
KW - bovine serum albumin
KW - liposomes
KW - osteosarcoma
KW - ponatinib
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U2 - 10.1021/acsabm.0c00685
DO - 10.1021/acsabm.0c00685
M3 - Article
VL - 3
SP - 6737
EP - 6745
JO - ACS Appl. Bio Mater.
JF - ACS Appl. Bio Mater.
IS - 10
ER -