Conjugation of Negatively Charged Cargo to Cell Surfaces for Advancement of Next-Generation Delivery Vehicles

Presenter

Alara Kilic

Campus

UMass Amherst

Sponsor

Michelle Farkas, Department of Chemistry, UMass Amherst

Schedule

Session 1, 10:30 AM - 11:15 AM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A77, Campus Center Auditorium, Row 4 (A61-A80) [Poster Location Map]

Abstract

The independent delivery of therapeutics to disease sites (e.g., cancer) is often less than ideal, resulting in off-target effects. For this reason, a variety of platforms are being developed as carriers. Cells have been promoted as vehicles for drug delivery over conventional carriers, such as nanoparticles. Whereas traditional vehicles rely on passive accumulation, resulting in suboptimal cargo buildup, cells respond to signals produced by and migrate towards tumors. Cell-based drug delivery commonly involves phagocytotic loading, which results in drug internalization. To have greater control over cargo loading and release, and for applications where internalization is not amenable (e.g., chemical sensing) the Farkas group approach seeks to modify surfaces of cells.

In my research, I am modifying model macrophages and stem cells with cyanine-5 (Cy5) derivative compounds using two different chemical reactions for attachment. Cy5 is a fluorophore that can be tracked, and I am specifically assessing the effects of different charges on the internalization of the cargo. Multiple Cy5 derivatives have been generated with different charges (0, -1, -2) and two chemical handles, hydrazides (for attachment to oxidized sialic acids) and N-hydroxysuccinimidyl esters (NHS; for attachment to amines). I hypothesize that increased charges will both improve solubility and help avoid internalization.

My results have indicated that the modifications are well-tolerated by the cells, with little difference observed depending on the reaction type used. I have found that while lack of negatively charged entities results in rapid internalization and that negative charges can diminish this, additional negative charge has minimal effects.

 

Keywords

Cell-Surface Modification, Cyanine-5 Derivate Compounds, Bioconjugation Reactions, Macrophages and Stem Cells , Cell-Based Drug Delivery

Research Area

Chemistry and Materials Science

SIMILAR ABSTRACTS (BY KEYWORD)