Overcoming the biological barriers to intravenous delivery of stem cells and drugs for the treatment of vascular-related diseases

Defective vasculature is one of the hallmarks of many diseases ranging from restricted blood flow in ischemia to abnormal blood vessel growth in cancer. Intravenous administration is particularly beneficial to patients with vascular-related diseases which are not easily accessible by the conventional methods. Therapeutics delivered via this route, however, must overcome the barriers along the way from the entry into the bloodstream to the target destination. To maximize the therapeutic efficacy, this dissertation investigates the use of polymeric nanoparticles to improve the transport of intravenously administered therapeutics and their accumulation in the diseased sites. The first part of this dissertation focuses on the delivery of mesenchymal stem cells to ischemic tissue. Chapter 2 presents the use of nanoparticles capable of enhancing the ability of stem cells to migrate across defective vascular walls. The surface of stem cells was tethered with particles that sustainably released stromal cell-derived factor-1α. Intravenously injected stem cells consequently exhibited a higher migration ability to ischemic muscle. The strategy of surface tethering was then applied towards protecting stem cells in the oxidative diseased sites, as presented in Chapter 3. The nanoparticles are devised to rapidly discharge antioxidant epigallocatechin gallate in response to elevated levels of hydrogen peroxide. The stem cells survived in sub-lethal concentrations of hydrogen peroxide and maintained their angiogenic potential in vivo. The second part of this dissertation looks at the delivery of doxorubicin to cancer cells. Chapter 4 presents the design strategies of nanoparticles for an enhanced release of entrapped doxorubicin within cancer cells. By incorporating moieties sensitive to the intracellular signals of cancer cells, drug release from the particles was significantly accelerated, giving rise to superior in vivo antitumor efficacy. Ultimately, the results of this dissertation will greatly contribute to improving the therapeutic outcome of numerous vascular-related diseases.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2018

Author dc:creator

• Teo, Jyeyng Yng

Contributors dc:contributor

• Kong, Hyunjoon
• Kraft, Mary L.
• Saif, Taher A.
• Yang, Yi Yan

• Mesenchymal stem cells
• transendothelial migration
• ischemia
• hydrogen peroxide
• cellular survival
• nanoparticles
• surface tethering
• cancer
• pH
• redox
• antitumor efficacy

Statement dc:rights

• Copyright 2018 Jye Yng Teo

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/101780

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/101780