Among the obstacles to successful breast cancer chemotherapy, three have been critical: problems of drug delivery, drug resistance, and cancer stem cells (CSCs). Until now, no effort has been made to address all three issues in a single approach. This proposal seeks to meet the challenge through a nanoplatform that we recently developed, which is comprised of a human serum albumin (HSA) coating, an amine-rich intermediate coating, and an iron oxide nanoparticle (lONP) core. It structurally resembles Abraxane, a commercial paclitaxel-HSA complex, but has smaller hydrodynamic size therefore better tumor accumulation rate and extravasation rate. Such favorable pharmacokinetics can be further improved by adding an external field at the tumor sites, making the nanoplatform a promising drug delivery vehicle. With superior ligand binding capability afforded by both the outer HSA and intermediate amine-rich layers, such nanoplatform can load a broad range of drug molecules. In this proposal, we plan to load such a nanoplatform with doxorubicin (or paclitaxel), salinomycin and tariquidar (or siRNA that targets the MDR-1 gene). Doxorubicin (or paclitaxel) is a chemotherapeutic agent that is commonly used in breast cancer therapy, directed toward killing the differentiated tumor cells that account for most of a tumor mass. Salinomycin is a recently identified therapeutic agent with selective CSC killing capability. Both tariquidar and siRNA can function as MDR-1 inhibitors and their modulating effects may lead to increased drug accumulation. It is hoped that, with complementary cancer killing mechanisms and favorable tumor targeting profile provided by the nanoplatform, this novel approach may lead to dramatically improved therapeutic effects. This will be the first investigation on tumor therapy to address problems of drug delivery, drug resistance, and CSCs in a single approach. Success of this study may be a milestone in breast cancer therapy for providing a powerful, all-inone, breast cancer therapeutic regimen.

Public Health Relevance

This proposal aims to load a novel nanoplatform with doxorubicin (or paclitaxel), salinomycin and MDR-1 modulator (tariquidar or siRNA that targets MDR-1 gene) and use the resulted nanoconjugates for combinational breast cancer therapy. The investigation is important for being the first time to address drug delivery, drug resistance and cancer stem cell (CSC) killing in a single breast cancer therapy approach.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Farrell, Dorothy F
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University of Georgia
Schools of Arts and Sciences
United States
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Chuang, Yen-Jun; Zhen, Zipeng; Zhang, Fan et al. (2014) Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging. Theranostics 4:1112-22
Tang, Wei; Zhen, Zipeng; Yang, Ce et al. (2014) Fe5C2 nanoparticles with high MRI contrast enhancement for tumor imaging. Small 10:1245-9
Wang, Luning; Tang, Wei; Zhen, Zipeng et al. (2014) Improving detection specificity of iron oxide nanoparticles (IONPs) using the SWIFT sequence with long T(2) suppression. Magn Reson Imaging 32:671-8
Chen, Hongmin; Wang, Geoffrey D; Tang, Wei et al. (2014) Gd-encapsulated carbonaceous dots with efficient renal clearance for magnetic resonance imaging. Adv Mater 26:6761-6
Zhen, Zipeng; Tang, Wei; Chuang, Yen-Jun et al. (2014) Tumor vasculature targeted photodynamic therapy for enhanced delivery of nanoparticles. ACS Nano 8:6004-13
Todd, Trever; Zhen, Zipeng; Tang, Wei et al. (2014) Iron oxide nanoparticle encapsulated diatoms for magnetic delivery of small molecules to tumors. Nanoscale 6:2073-6
Zhen, Zipeng; Tang, Wei; Guo, Cunlan et al. (2013) Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer. ACS Nano 7:6988-96
Zhen, Zipeng; Tang, Wei; Chen, Hongmin et al. (2013) RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 7:4830-7
Cowger, Taku; Xie, Jin (2013) Polyaspartic acid coated iron oxide nanoprobes for PET/MRI imaging. Methods Mol Biol 1025:225-35
Chen, Hongmin; Zhen, Zipeng; Tang, Wei et al. (2013) Label-free luminescent mesoporous silica nanoparticles for imaging and drug delivery. Theranostics 3:650-7

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