Reproducible and Characterized Method for Ponatinib Encapsulation into Biomimetic Lipid Nanoparticles as a Platform for Multi-Tyrosine Kinase-Targeted Therapy

Abstract

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.

Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury

“…[ 18 ] Several nanoformulations have been developed in recent decades to improve the solubility and pharmacokinetics of different drugs, improving drug targeting to reduce side effects. [ 19 ] However, brain‐targeted nanotherapeutics have numerous biological roadblocks, such as their inability to cross the BBB, uptake by the mononuclear phagocyte system, elimination by Kupffer cells in the liver, and glomerular filtration in the kidneys before reaching their target zone. [ 20 ] Biomimetic strategies represent a paradigm shift in NP design, enabling next‐generation platforms to interact and effectively affect the behavior of complex biological systems.…”

Humanized Biomimetic Nanovesicles for Neuron Targeting

“…Next, two distinct lipid formulations were tested to enable the encapsulation of different potential therapeutic cargo (Table S1 , Supporting Information). Lipid formulation A (i.e., L A , N A , and P A ) was designed for the delivery of either proteins [ 35 ] or small hydrophobic [ 27 , 34 , 35 ] or hydrophilic drugs. [ 36 ] It consisted of neutral lipids 1,2‐dipalmitoyl‐ sn ‐glycero‐3‐phosphocholine (DPPC), 1,2‐dioleoyl‐ sn ‐glycero‐3‐phosphocholine (DOPC), and cholesterol.…”

“…Cryo-TEM of NVs: NVs solutions were vitrified and imaged at the Baylor College of Medicine Cryo-Electron Microscopy Core Facility (Houston TX) as reported by Zinger et al [35] Briefly, Quantifoil R2/1, 200 Cu mesh Holey carbon grids were pretreated with airglow discharge for 45 s to make the carbon surface hydrophilic. In addition, Quantifoil R2/1 200 Cu +4 nm thin carbon grids were also glow discharged for 10 s to test the efficacy of the added layer of continuous carbon with the binding of the NVs.…”

Nanotechnology of Tyrosine Kinase Inhibitors in Cancer Therapy: A Perspective

“…Targeted Ponatinib-loaded NPs have been recently investigated to evaluate their biological effect on osteosarcoma cell lines. In detail, Zinger et al [ 145 ] reported the design and synthesis of biomimetic/targeted NPs incorporating Ponatinib. These SLNs incorporate membrane proteins purified from activated leukocytes that enable immune evasion and enhanced targeting of inflamed endothelium.…”