Hsing-Wen Sung, Ph.D.
Tsing Hua Chair Professor
Department of Chemical Engineering
Director
Institute of Biomedical Engineering
Email: hwsung@che.nthu.edu.tw
Hsing-Wen Sung is a Tsing Hua Chair Professor, Department of Chemical Engineering and the Director of Institute of Biomedical Engineering, National Tisng Hua University. He received his PhD degree from Department of Chemical Engineering and Biomedical Engineering Center, Georgia Institute of Technology in May 1988. His research interests are nanobiomaterials, nanomedicine, drug/gene delivery, and tissue engineering. Professor Sung has received numerous awards such as Fellow of American Institute for Medical and Biological Engineering, Fellow of International Union of Societies for Biomaterials Science and Engineering, Academician of Asia Pacific Academy of Materials, Ho Chin Tui Outstanding Research Award, National Science Council Outstanding Research Award, and Professor Tsai-The Lai Award. He has published 220 scientific papers and received 70 international patents.
1 Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan
2 Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
3 Department of Orthopedics, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
4 Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
5 Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
In this work, two bubble-generating agents, ammonium bicarbonate (ABC) and sodium bicarbonate (SBC) that can generate CO2 bubbles, are separately encapsulated in carrier systems for actively triggering drug release locally. Widely recognized for their ability to increase intratumoral accumulation, PEGylated liposomes are employed as stable vehicles for carrying doxorubicin (DOX; Doxil®). However, the slow and passive drug release from the Doxil® formulation significantly inhibits its antitumor efficacy. To resolve this problem, our group develops a thermoresponsive liposomal formulation. As the key component of this liposomal formulation, its encapsulated ABC creates the transmembrane gradient needed for a highly efficient DOX encapsulation. Moreover, at a high temperature of roughly 42°C, ABC decomposition generates CO2 bubbles, subsequently creating permeable defects in the lipid bilayer and ultimately inducing a rapid DOX release to instantly increase the drug concentration locally. The feasibility of using this thermoresponsive bubble-generating liposomal system for tumor-specific chemotherapy under mild hyperthermia is investigated. The in vitro drug-release profiles are quantified from test liposomes under mild hyperthermia conditions. Their in vivo biodistribution, pharmacokinetics, drug accumulation, and antitumor activity against locally heated tumors are examined as well. We also develop hollow microspheres (HMs) that can deliver anticancer drug into tumor cells and quickly release the drug in an acidic organelle such as lysosome. The HMs are fabricated from PLGA using a double-emulsion method, with the aqueous core containing DOX and SBC. In acidic environments, SBC reacts with the acid to quickly generate CO2 bubbles, triggering the shell of the HMs to disrupt, thereby quickly releasing DOX locally and causing the cells to die. These highly stimuli-responsive carrier systems contribute to efforts to establish effective tumor-selective chemotherapy.