Download Cellular Delivery of Therapeutics to Tumor Hypoxia 腫瘤缺氧區的

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.