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TEM image of the unimolecular micelles.

Multifunctional Unimolecular Micelles for Targeted Cancer Therapy Shaoqin “Sarah” Gong, University of Wisconsin-Madison, DMR 032187.

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TEM image of the unimolecular micelles.

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  1. Multifunctional Unimolecular Micelles for Targeted Cancer TherapyShaoqin “Sarah” Gong, University of Wisconsin-Madison, DMR 032187 • Tumor-targeting multifunctional unimolecular micelles that exhibit a pH-triggered drug release profile and excellent in vivo stability were developed for targeted cancer chemotherapy. • The unimolecular micelles were formed by hyperbranchedamphiphilic H40-(poly(γ-benzyl-L-glutamate) (PBLG)-Hydrazone (Hyd)-DOX)-MPEG/PEG-cRGDcopolymers. • The hydrodynamic diameters of the unimolecular micelles were around 50 nm. • The cellular uptake of the cRGD-conjugated unimolecular micelles was much higher than that of the non-targeted unimolecular micelles resulting from receptor-mediated endocytosis, thereby leading to much higher cytotoxicity. • cRGD-conjugated unimolecular micelles demonstrated a much higher in vivo tumor (U87MG) biodistribution than non-conjugated ones. DOX conjugated hydrophilic by pH-sensitive bond outer PEG shell hydrophobic inner core Tumor-targeting ligand Hydrophilic PEG segment Hydrophobic PBLG segment • Hyperbranched polyester core (H40) • DOX conjugated by pH-sensitive bond Active tumor targeting ligand (cRGD) PET 64Cu chelator NOTA Schematic structure of unimolecular micelle based on hyper-branched H40-PBLG-Hyd-DOX-MPEG/PEG-cRGD copolymer. TEM image of the unimolecularmicelles. PET imaging of the in vivo biodistribution of the micelles

  2. Multifunctional Unimolecular Micelles for Targeted Cancer TherapyShaoqin “Sarah” Gong, University of Wisconsin-Madison, DMR 1032187 • Cancer is the leading cause of death worldwide and the second leading cause of death in the U.S. More than 20,000 people die each day from various types of cancer. Because traditional chemotherapy is systemic, it can cause serious, undesirable side-effects and low treatment efficacy. • Nanotechnology can potentially revolutionize cancer therapy and diagnosis. Various nanoparticles--including liposomes, polymer micelles, and vesicles--have been studied as drug nanocarriers for targeted cancer therapy. One drawback with the most widely studied drug nanocarriers formed by self-assembly is their relatively poor in vivo stability due to their dynamic nature. • Anticancer drugs conjugated onto unimolecular micelles (i.e., micelles formed by a single multi-arm amphiphilic block copolymer molecule) via pH-sensitive linkage can potentially provide excellent in vivo stability, which is highly desirable for targeted cancer therapy. • The resulting knowledge was integrated into a new course created by the PI related to Bio-Nano-Materials for the Spring 2011 semester. • Efforts were made to support graduate students from underrepresented groups. Currently, there are two female researchers working on this project. • The Co-PI’s lab has hosted several high school students in recent years, including a female high school student last summer.

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