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Cellular Delivery of Therapeutics to Tumor Hypoxia 腫瘤缺氧區的細胞式治療傳輸 邱信程 國立清華大學 生醫工程與環境科學系 Hsin-Cheng Chiu, Ph.D. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan Overcoming difficulties often encountered in nanomedicine delivery to solid tumor hypoxia regions remains a great challenge. This is primarily because of the void of blood microvessels in these regions, thereby leading to severe limitation in transportation of therapeutics into deep tumor tissues. To address this issue, adopting bone marrow-derived monocytes capable of being chemotactically recruited towards tumor hypoxia to serve as a cellular Trojan for active targeted delivery is a promising strategy to improve accumulation of therapeutics in tumor avascular regions. To this end, we have developed a lipid-containing copolymer system comprising acrylic acid and distearin acrylate for the preparation of various supramolecular assemblies in polymersome and/or microbubble structures as depots for C5F12, oxygen and various therapies, respectively. The high lipidcontaining copolymers exhibit an excellent capability undergoing spontaneous assembly in aqueous phases into the hollow spherical architectures featured with highly impermeable polymeric membranes to prevent therapeutics or echogenic gaseous cargos from premature leakage. Two approaches presented herein demonstrate the potential of cell-based delivery for improving chemotherapy or photodynamic therapy (PDT) on tumor hypoxia. For cellbased chemotherapy, the results confirmed successful cellular transport of therapeutic payloads to tumor hypoxic regions and pronounced chemotherapeutic action against hypoxic cancer cells through the remote-controlled drug liberation from cellular hosts in vivo. The chemotactic behavior of therapeutic monocytes towards tumor hypoxia also gave rise to the highly enhanced chemotherapy efficacy on the tumor-bearing mice pretreated with -irradiation, known as an external energy to disrupt blood supply to tumors and thus the therapeutics transport via blood circulation. For cell-based PDT, an innovative strategy for overcoming the limitation of PDT in tumor hypoxia using tumortropic monocytes for delivery of oxygen together with photosensitizer in polymer bubbles was demonstrated. The histological examinations of tumor sections showed the pronounced antitumor effect elicited by PDT along with additional oxygen supply in tumor hypoxic regions. Our results demonstrate the great promise of cellular delivery for improving therapeutic efficacy in tumor hypoxia.