Bioconjugated β-Cyclodextrin-Perfluorohexane Nanocone Clusters as Functional Nanoparticles for Nanoparticle-Mediated
Cemran Toydemir, Sarah Hall1, Erhan Demirel
1Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia24061, United States.
Biomacromolecules
|November 23, 2022
Summary
New nanocone clusters (NCCs) improve nanoparticle-mediated histotripsy (NMH) by enabling targeted therapies. These functionalized NCCs lower cavitation thresholds, enhancing NMH
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Nanocone clusters (NCCs) are advanced agents for nanoparticle-mediated histotripsy (NMH), overcoming limitations of earlier nanodroplets.
- NCCs are formed from FDA-approved cyclodextrins (CDs) and perfluorocarbons (PFCs), offering improved stability and storage as powders.
- Beta-cyclodextrin (βCD) and perfluorohexane (PFH) are optimal for NCC formation due to their properties.
Purpose of the Study:
- To develop functionalized NCCs for enhanced NMH therapy.
- To demonstrate the bioconjugation potential of NCCs via targeting, PEGylation, and fluorescent labeling.
- To validate the efficacy of bioconjugated NCCs in lowering the histotripsy cavitation threshold.
Main Methods:
- Monofunctionalization of βCD with azide, alkyne, and amine groups for subsequent coupling reactions.
- Synthesis of functional NCCs using monofunctionalized βCD and PFH.
- Bioconjugation of NCCs with EPPT1 peptide, folic acid (FA), and PEGylation.
- Fluorescent labeling of NCCs using fluorescein isothiocyanate (FITC).
Main Results:
- Successfully synthesized functional NCCs via click chemistry and EDC/NHS coupling.
- Demonstrated successful bioconjugation with targeting agents (EPPT1, FA) and PEGylation.
- Achieved fluorescently labeled NCCs using FITC.
- All bioconjugated NCCs effectively reduced the histotripsy cavitation threshold in vitro.
Conclusions:
- Functionalized NCCs are promising precursors for bioconjugation in NMH.
- Bioconjugated NCCs enhance NMH by lowering cavitation thresholds and enabling targeted delivery.
- These advanced NCCs represent improved tools for targeted noninvasive ablation therapies.
