Fighting cancer with nanomedicine−drug-polyester nanoconjugates for targeted cancer therapy

Yin, Qian

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https://hdl.handle.net/2142/87988 Copy

Description

Title

Fighting cancer with nanomedicine−drug-polyester nanoconjugates for targeted cancer therapy

Author(s)

Yin, Qian

Issue Date

2015-07-01

Director of Research (if dissertation) or Advisor (if thesis)

Cheng, Jianjun

Doctoral Committee Chair(s)

Cheng, Jianjun

Committee Member(s)

• Fan, Timothy M.
• Braun, Paul V.
• Lu, Yi
• Kilian, Kristopher A.

Department of Study

Materials Science & Engineerng

Discipline

Materials Science & Engr

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Nanoparticle
• Polyester
• Cancer Therapy
• Cancer diagnosis
• Cancer targeting
• Molecular imaging

Abstract

The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.

Graduation Semester

2015-8

Type of Resource

text

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Copyright and License Information

Copyright 2015 Qian Yin

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