Date of Award

2016

Document Type

Open Access Dissertation

Department

College of Pharmacy

First Advisor

Peisheng Xu

Abstract

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve their anticancer efficacy as well decrease adverse effects.

We firstly developed a poly[(2-(pyridin-2-yldisulfanyl)ethyl acrylate)-co- [poly(ethylene glycol)]] (PDA-PEG) polymer and found that this polymer when combined with copper could efficiently kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. Next, we used this polymer or its derivatives to fabricate a series of stimuli responsive nanogels for targeted photodynamic therapy (PDT). These nanogels could efficiently target tumors under the help of targeting ligands and control photosensitizers release in the tumor by response to pH, redox potential and temperature, and finally induce high anticancer efficacy.

To further improve the therapeutic efficacy, a polydopamine coated poly(lacticco- glycolic acid) nanoparticle was developed for chemo-thermal therapy. This nanoparticle could respond to near infrared light (NIR) to release the anticancer drug (doxorubicin) in the tumor and effectively eradicate head and neck tumor in a xenograft mouse model by combining the NIR-mediated photothermal therapy and doxorubicin induced chemotherapy.

Rights

© 2016, Huacheng He

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