Localized and disease-selective drug delivery using adhesive hydrogels for treatment of locally advanced TNBC
Name
958998241-MIT.pdf
Description
Full printable version
Size
14.74 MB
Format
Adobe PDF
Checksum (MD5)
d01a125cf868210f118d497ca61b49c6
Author(s)
Oliva Jorge, Nuria
Advisor(s)
Elazer R. Edelman and Natalie Artzi.
Date Issued
2016
Publisher
Massachusetts Institute of Technology
Abstract
Triple negative breast cancer (TNBC) is an aggressive form of cancer that represents 20% of invasive breast cancers, and about 15% are locally advanced at time of presentation. TNBC is negative for estrogen and progesterone receptor, as well as for HER2, and hence it is not treatable with common endocrine treatment such as tamoxifen or Herceptin. Systemic neoadjuvant therapy has been established as the preferred therapeutic approach for locally advanced breast cancer, downstaging the disease and preventing mastectomy. However, complications of systemic chemotherapy are devastating. Local therapy would prevent high concentrations of circulating drug and reduce off-target tissue retention. Yet, the means to attain ideal release kinetics and selective uptake remain elusive. I developed a novel class of biocompatible and biodegradable adhesive materials based on dendrimer and dextran that can coat the tumor and locally release doxorubicin in a controlled manner. Doxorubicin was conjugated to the dendritic component of the adhesive hydrogel to form a pro-drug capable of being released over time as the hydrogel degrades at a pre-programmed rate. The pro-drug was further modified with a ligand capable of sensing and discerning between healthy and cancer cells and facilitating uptake through receptor-mediated endocytosis (RME). The platform developed herein provides a paradigm shift in the way we treat cancer, in a local, selective and targeted manner, to impart optimal clinical outcome.
Description
Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 111-117).
Subjects
Harvard--MIT Program in Health Sciences and Technology.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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