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TEM image of the unimolecular micelles based on H40-(PMA-Hyd-DOX- co -PCL)-MPEG/PEG-FA polymer.

Multifunctional Unimolecular Micelles for Targeted Cancer Therapy Shaoqin Gong, University of Wisconsin-Milwaukee, DMR 0906641.

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TEM image of the unimolecular micelles based on H40-(PMA-Hyd-DOX- co -PCL)-MPEG/PEG-FA polymer.

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  1. Multifunctional Unimolecular Micelles for Targeted Cancer TherapyShaoqin Gong, University of Wisconsin-Milwaukee, DMR 0906641 • 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 20-arm hyperbranched amphiphilic H40-(PMA-Hyd-DOX-co-PCL)-MPEG/PEG-FA copolymers. • The hydrodynamic diameter of the unimolecular micelles was 25  2 nm, determined by DLS. • The DOX loading content was 14.2 %. • The cellular uptake of the FA-conjugated unimolecular micelles was much higher than that of the non-targeted unimolecular micelles resulting from FA-receptor-mediated endocytosis, thereby leading to much higher cytotoxicity. • These unique unimolecular micelles may provide a very promising approach for targeted cancer therapy. • Yang, X., Grailer, J. J., Pilla, S., Steeber, D. A., Gong, S., Bioconjugate Chemistry, 21, pp.496-504(2010). Schematic structure of unimolecular micelle based on H40-(poly(β-malic acid)-hydrazone-Doxorubicin-co-poly(ε-caprolactone))-methoxy-poly(ethylene glycol)-poly(ethylene glycol)-folate (H40-(PMA-Hyd-DOX-co-PCL)-MPEG/PEG-FA) polymer. TEM image of the unimolecular micelles based on H40-(PMA-Hyd-DOX-co-PCL)-MPEG/PEG-FA polymer.

  2. Multifunctional Unimolecular Micelles for Targeted Cancer Therapy Shaoqin Gong, University of Wisconsin-Milwaukee, DMR 0906641 • 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. Traditional chemotherapy is systemic which may 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 common drawback with these most widely studied drug nanocarriers formed by self-assembly is their relatively poor in vivo stability due to their dynamic nature. • Anticancer drug conjugated onto unimolecular micelles (i.e., micelle 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 will be 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 graduate students 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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