방사선의학 웹진

바로가기  >

Abstract

Designing nanocarriers with active targeting has been increasingly emphasized as for an ideal delivery mechanism of anti-cancer therapeutic agents, but the actualization has been constrained by lack of reliable strategy ultimately applicable. Here, we designed and verified a strategy to achieve active targeting nanomedicine that works in a living body, utilizing animal models bearing a patient's tumor tissue and subjected to the same treatments that would be used in the clinic. The concept for this strategy was that a novel peptide probe and its counterpart protein, which responded to a therapy, were identified, and then the inherent ability of the peptide to target the designated tumor protein was used for active targeting in vivo. An initial dose of ionizing radiation was locally delivered to the gastric cancer (GC) tumor of a patient-derived xenograft mouse model, and phage-displayed peptide library was intravenously injected. The peptides tightly bound to the tumor were recovered, and the counterpart protein was subsequently identified. Peptide-conjugated liposomal drug showed dramatically improved therapeutic efficacy and possibility of diagnostic imaging with radiation. These results strongly suggested the potential of our strategy to achieve in vivo functional active targeting and to be applied clinically for human cancer treatment.

Author information

Lee KJ1, Shin SH1, Lee JH1, Ju EJ1, Park YY2, Hwang JJ3, Suh YA4, Hong SM5, Jang SJ6, Lee JS7, Song SY8, Jeong SY9, Choi EK10.

1Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.2Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.3Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.4Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.6Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.7Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.8Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address: coocoori@amc.seoul.kr.9Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address: syj@amc.seoul.kr.10Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address: ekchoi@amc.seoul.kr.