CBE Seminar: Desiree Denman & Ajay Dwivedi

Desiree Denman's Abstract

Polyethylene glycol (PEG) is a common polymer in therapeutic nanoparticles (NPs),

enabling applications from chemotherapy to m

RNA vaccines. Understanding how PEG

interacts with mammalian proteins and cells remains a critical need. The prevailing

model holds that PEG triggers anti-PEG antibodies, which bind the NP and recruit

additional serum proteins, including complement. This complex engages receptors on

professional phagocytes such as macrophages, leading to rapid clearance from

circulation. This phenomenon, termed accelerated blood clearance (ABC), limits the

efficacy of PEG-NPs in applications requiring repeated dosing.

I hypothesize that this paradigm inadequately explains PEG-NP biodistribution and

thus clearance. To test this, I will determine the biodistribution of two types of PEG-NPs

in mice: (1) PEG micelles and (2) PE

Gylated liposomes ("DOXEBO"). I will identify the

signaling pathways that PEG micelles activate in macrophages. My preliminary data

show that PEG micelles generate anti-PEG IgM antibodies, but these antibodies bind

the micelles weakly and do not strongly affect their clearance. These findings support

my hypothesis that PEG-NPs are not always cleared by the antibodies produced

against them.

The overall hypothesis of this proposal is that PEG micelle NPs escape ABC and

trigger non-inflammatory cellular signaling pathways. These attributes make them ideal

for long-term drug delivery. Aim 1 will characterize anti-PEG IgM kinetics, magnitude,

and affinity for spherical and cylindrical micelles, with DOXEBO as a positive control,

using ELISA, and pull-down assays. This aim will determine whether geometry affects

ABC upon repeated dosing. Aim 2 will elucidate micelle-specific macrophage receptor

engagement and signaling using DIA-MS phosphoproteomics, ELISA, and western

blot. This aim will identify which receptors mediate uptake and which pathways each

geometry activates. Aim 3 will compare spherical and cylindrical micelle organ

biodistribution profiles using IVIS imaging of fluorescently labeled micelles, with ex vivo

radiant efficiency quantifying per-organ uptake. This aim will reveal whether geometry

directs micelle accumulation toward clearance organs such as the liver.

Together, these experiments will establish how nanoparticle geometry controls

receptor-mediated clearance independently of antibody opsonization. By

distinguishing geometry-driven from antibody-driven clearance, this work addresses a

fundamental gap in nanomedicine and supports micelle-based carriers for chronic

therapies.

Ajay Dwivedi's Abstract

Understanding the relationship between ion coordination, molecular interactions, and transport properties is essential for designing efficient electrolytes for next-generation energy storage technologies. Polymer–ionic liquid-salt based electrolytes offer promising opportunities for tailoring these properties through variations in metal-ion and salt loading. In this seminar, I wi