Ionic Liquid-Grafted Alginate as a Tunable Biomaterial for Nanoparticle Anti-Cancer Drug Delivery
Hamadani, Christine Tanner, Eden Oldinski, Rachael
Hamadani, Christine
Tanner, Eden
Oldinski, Rachael
Citations
Altmetric:
License
License
Abstract
Nanoparticle (NP) mediated chemotherapeutic delivery overcomes adverse events encountered in traditional pharmaceutical administration via sustained, targeted delivery. Unfortunately, few NPs are clinically approved due to: 1) inconsistent cancer cell affinity/uptake, and 2) immune-mediated clearance from unwanted NP surface modification by opsonins. Recently, we demonstrated cancer cell internalization of PEG-neutralized calcium-cross linked alginate NPs for stealth delivery of FGF-2 without receptor activation, selectively inducing apoptosis without affecting nontransformed cells. We now enhance this vehicle design and prepare it for biocompatible systemic delivery by eliminating potentially immunogenic PEG and toxic cross-linking procedures, producing smaller consistent nanoparticle sizes, shielding NP surfaces from opsonization in circulation, and enhancing NP uptake. Herein, we present poly-ionic hybrid NPs composed of electrostatically grafted ionic liquid (IL) (i.e., protein-phobic anionic, cell membrane-penetrative cationic) to alginate (IL-Alg NPs). Short-chain unsaturated fatty acid anionic structures have demonstrated protein-phobicity against opsonins, and specific cationic structures have shown promise in cell membrane permeation. We hypothesize that IL-Alg NPs may be engineered to expose tri-functional NP surface sites that: 1) limit serum protein-NP interactions; 2) modulate NP uptake efficiency by cancer cells via tunable surface charge and cation-structure mediated cell-membrane permeation; 3) control intracellular drug delivery from alginate-cation-anion electrostatic junctions. Preliminary in vitro characterization infers NPs can be optimized by physicochemically coordinating the IL-alginate bulk graft during synthesis. In conclusion, IL-Alg NPs exhibit potential for IV-administered delivery of FGF-2 to treat cancer.
Description
Date
2020-01-01
Student Status
Graduate
Journal Title
Journal ISSN
Volume Title
Type of presentation
virtual-oral-presentation
Collections
Research Projects
Organizational Units
Journal Issue
Citation
DOI
Department
Program/Major
Biomedical Engineering
Biomedical Engineering
Biomedical Engineering
College/School
Larner College of Medicine
College of Engineering and Mathematical Sciences
College of Engineering and Mathematical Sciences
Organization
item.page.researchcategory
Engineering & Physical Sciences
Health Sciences
Health Sciences