Presentation Title

Ionic Liquid-Grafted Alginate as a Tunable Biomaterial for Nanoparticle Anti-Cancer Drug Delivery

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.

Primary Faculty Mentor Name

Dr. Rachael Oldinski, Ph.D.

Secondary Mentor Name

Dr. Eden Tanner, Ph.D.

Faculty/Staff Collaborators

Dr. Amber Doiron, Ph.D. (BME faculty, UVM), Lydia Axelrod (Undergraduate Research Assistant, UVM), Shefa (Ceres) Rafiq (Ph.D. Candidate/Graduate Assistant, UVM)

Status

Graduate

Student College

College of Engineering and Mathematical Sciences

Second Student College

Larner College of Medicine

Program/Major

Biomedical Engineering

Second Program/Major

Biomedical Engineering

Primary Research Category

Engineering & Physical Sciences

Secondary Research Category

Health Sciences

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Ionic Liquid-Grafted Alginate as a Tunable Biomaterial for Nanoparticle Anti-Cancer Drug Delivery

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.