Biomaterials and Tissue Engineering Research Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences
Multifunctional Polymeric Nanoparticles for Targeted Cancer Therapy and Diagnosis
Speaker：Prof. Shaoqin Sarah Gong
(University of Wisconsin-Madison)
Shaoqin Sarah Gong is a Vilas Distinguished Achievement Professor in the Department of Biomedical Engineering and the Wisconsin Institutes for Discovery at the University of Wisconsin–Madison. She received her BA and MS degrees from Tsinghua University and her PhD degree from the University of Michigan–Ann Arbor—all in Materials Science and Engineering. Prof. Gong has co-authored over 120 peer-reviewed journal articles and more than 120 conference papers. She is an editorial board member for several journals including Biomaterials, Biofabrication, Theranostics, Nanotheranostics, and the Journal of Biobased Materials and Bioenergy. She also served as an Associate Editor for Biomaterials and is a winner of a number of awards including the NSF CAREER Award and NIH Career Development Award. Prof. Gong’s current research focuses on the development of multifunctional nanomaterials including nanomedicines and polymer nanocomposites for various applications. In the area of nanomedicines, her research group has developed a series of multifunctional drug/agent nanocarriers including unimolecular micelles, polymer vesicles, and polymer-functionalized inorganic nanoparticles (e.g., gold, superparamagnetic iron oxide, upconversion nanoparticles) for targeted drug/agent delivery to treat and monitor various major health threats including cancers, vascular disorders, and eye diseases. In the area of polymer nanocomposites, her research group has developed a series of stimuli-responsive polymer nanocomposites and high-performance, environmentally friendly biobased materials.
Drug nanocarriers are of great interest in targeted cancer therapy due to their passive (via the enhanced permeability and retention (EPR) effect) and active (via cell-specific ligand conjugation) tumor-targeting capabilities. Conventional polymer micelles, formed by the self-assembling of multiple linear block copolymers, are one of the most studied nanoplatform. However, one major concern with these conventional polymer micelles is their poor in vivo stability due to the dynamic nature of the self-assembly process. Premature rupture of these drug nanocarriers during circulation can cause a burst release of payload into the bloodstream, which can cause potential systemic toxicity and surrender their tumor-targeting ability, thereby limiting their in vivo application. Unimolecular micelles—formed by individual multi-arm star amphiphilic block copolymers—have been investigated to overcome this problem. Because of their covalent nature and unique chemical structure, properly engineered unimolecular micelles can possess excellent in vivo stability. Moreover, due to their superior chemical versatility, these unique unimolecular micelles have been successfully functionalized with different targeting ligands (e.g. small molecules, peptides, antibodies, and aptamers) and imaging probes (e.g., dyes, radioisotopes, etc.). In particular, a multifunctional unimolecular micelle was developed for targeted triple-negative breast cancer (TNBC) therapy. The unimolecular micelles were loaded with aminoflavone (AF; an anticancer drug) and conjugated with GE11, an EGFR-binding peptide targeting epidermal growth factor receptor (EGFR) that is frequently overexpressed in TNBC tumors. These AF-loaded and GE11-conjugated unimolecular micelles induced tumor regression in an orthotopic xenograft model. In addition, a thailandepsin-A (TDP-A; an HDAC inhibitor)-loaded and KE108-conjugated unimolecular micelle was designed for targeted neuroendocrine cancer (NE) therapy. KE108 peptide, a somatostatin analog possessing high affinity for all five subtypes of somatostatin receptors commonly overexpressed in NE cancer cells, was used for the first time as an NE-cancer-targeting ligand, and exhibited superior targeting abilities compared to other common somatostatin analogs, such as octreotide. TDP-A-loaded and KE108-conjugated micelles induced the highest anticancer efficacy among all control groups without any detectable systemic toxicity. In addition, polymer functionalized inorganic nanoparticles including up conversion nanoparticles (UCNPs) capable of light-controlled combinational chemotherapy and photodynamic therapy as well as in vivo fluorescence imaging will also be discussed briefly.