Synergistic development of an engineered biodegradable theranostic probe and lymph node organ-on-a-chip to study nanoparticle-lymphatic interactions

The lymphatic system plays a vital role in controlling immune response. Despite this, cancer often reshapes the lymphatic microenvironment and metastasizes into lymph nodes. Theranostic (therapeutic + diagnostic) nanoparticles have been used in a variety of applications, including the detection and treatment of cancer metastases in lymph nodes. However, accumulation in the liver remains a major concern with any nanoparticle-based intervention. We have developed biodegradable nanoparticles made of biliverdin, an endogenous fluorophore that results from the breakdown of hemoglobin. We demonstrated the degradation of biliverdin nanoparticles (BVNPs) in the presence of biliverdin reductase, as well as the use of BVNPs in photoacoustic imaging of sentinel lymph nodes. Fundamental studies on BVNPs demonstrated shifts in their spectral properties as a response to various stimuli, including pH changes, metal chelation, and UV irradiation. BVNPs loaded with doxorubicin (Dox-BVNPs) were used for treatment of triple-negative breast cancer. BVNPs were further modified via metal chelation for use as a magnetic resonance imaging contrast agent. Finally, hybrid biliverdin-silica particles were developed for use in fluorescence imaging in the near-infrared I and II windows. At the same time, microfluidic models were created to recapitulate the lymph node tissue microenvironment. We first developed a lymphatic vessel on-a-chip that achieved long-term culture of primary human lymphatic endothelial cells (HLECs) under gravity-driven flow. We then developed a lymphatic system on-a-chip, comprised of multiple units that each model the lymph node subscapsular sinus, high endothelial venules, and lymph nodules. This device allows for the exploration of transport of nanoparticles, cancer cells, and immune cells to and from lymph nodes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Fathi, Parinaz

Contributors dc:contributor

• Pan, Dipanjan
• Esch, Mandy
• Nie, Shuming
• Underhill, Gregory
• Chan, Jefferson

• biliverdin, nanoparticle, lymph node, lymphatic, tissue-chip, organ-chip, photoacoustic imaging, fluorescence imaging, MR imaging, near-infrared

Statement dc:rights

• Copyright Parinaz Fathi 2020

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108656

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108656