Home
Resource
A clickable, free radical-responsive biomaterial for targeted delivery applications
PDF
PDF format is widely accepted and good for printing.
Plug-in required
Access to this PDF has been restricted at the author's request. It will be publicly available after April 27, 2025.
Citation & Export
View Usage Statistics
Staff View

Citation & Export
Hide

Simple citation

DiMartini, Emily T.. A clickable, free radical-responsive biomaterial for targeted delivery applications. Retrieved from https://doi.org/doi:10.7282/t3-menw-a066

Export

Click here for information about Citation Management Tools at Rutgers.

Statistics
Hide

Description

TitleA clickable, free radical-responsive biomaterial for targeted delivery applications
NameDiMartini, Emily T. (author); Shreiber, David (chair); Gormley, Adam (member); Parekkadan, Biju (member); Minko, Tamara (member); Rutgers University; School of Graduate Studies
Date Created2023
Other Date2023-05 (degree)
SubjectBiomedical engineering, Drug delivery systems, Biomedical materials
Extent129 pages : illustrations
DescriptionMany therapies are limited by poor bioavailability and toxic side effects in off-target tissues. Stimuli-responsive delivery systems are an emerging strategy to target drugs to disease sites and mitigate side effects. These systems leverage common pathophysiological triggers, such as free radicals, and are amenable to many diseases. Native free radicals are vital to normal physiological processes but are upregulated in many diseases, and the overproduction of reactive oxygen species (ROS) results in cellular damage. In chemical synthesis, free radicals are frequently used to control polymerization and crosslinking via acrylate functional chemistries. We have hypothesized that these radical-sensitive materials, such as polyethylene glycol diacrylate (PEGDA), can also be used to target drug delivery by selectively crosslinking polymers at disease sites with high radical levels to locally accumulate a coupled payload. Our preliminary results demonstrated that (1) physiologically-relevant free radicals are capable of forming acrylate-acrylate crosslinks, (2) the resulting polymer network and payload is sustained in a tissue mimic model, and (3) the crosslinking reaction consumed radicals to directly protect fibroblasts and improve viability. In this dissertation, we studied the free radical-initiated delivery system in vivo and characterized alternative terminal polymer chemistries in vitro. In a tumor animal model, intratumorally-administered acrylated polymers sustained fluorescent payloads relative to non-acrylated controls. Alternative chemistries were characterized in collagen gels, and similar to acrylates, PEG dithiols and PEG dialkenes immobilized payloads upon ROS exposure. These alternative chemistry studies inspired us to develop a two-step catch-and-release system. The majority of this thesis was dedicated to developing the two-phase system in cell-free and tissue equivalent models, leveraging the azide-DBCO click chemistry reaction to allow payload delivery to occur after the formation of a capture net. The azide click component is included with radical-sensitive PEGDA, and the payload is conjugated to the bioorthogonal DBCO group for delivery. Matrix metalloproteinase (MMP) enzymes are broadly upregulated in disease, and we incorporated enzymatically-degradable peptide sequences into polymer backbones to engineer release. Azide pre-targeting allowed precise control over the timing and amount of payload that was delivered, which improves the flexibility and versatility of the targeting system. Payloads were released from capture nets using the enzymatically-degradable polymers, which can facilitate local transport and interactions with nearby cells. Taken together, this research demonstrates proof-of-principle for a responsive and clickable biomaterial to serve as a multi-potent agent for disease treatment.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/t3-menw-a066
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Version 8.5.5
Rutgers University Libraries - Copyright ©2024