방사선생물학

본문글자크기
  • [Biomaterials.] A Novel Nanoparticle-Based Theranostic Agent Targeting LRP-1 Enhances the Efficacy of Neoadjuvant Radiotherapy in Colorectal Cancer

    울산의대 / 이경진, 최은경*

  • 출처
    Biomaterials.
  • 등재일
    2020 May 27
  • 저널이슈번호
    255:120151. doi: 10.1016/j.biomaterials.2020.120151. Online ahead of print.
  • 내용

    바로가기  >

    Abstract
    Neoadjuvant radiotherapy has become an important therapeutic option for colorectal cancer (CRC) patients, whereas complete tumor response is observed only in 20-30% patients. Therefore, the development of diagnostic probe for radio-resistance is important to decide an optimal treatment timing and strategy for radiotherapy-resistant CRC patients. In this study, using the patient-derived xenograft (PDX) mouse model established with a radio-resistant CRC tumor tissue, we found low-density lipoprotein receptor-related protein-1 (LRP-1) as a radio-resistant marker protein induced by initial-dose radiation in radio-resistant CRC tumors. Simultaneously, we discovered a LRP-1 targeting peptide in a radio-resistant CRC PDX through in vivo peptide screening. We next engineered the theranostic agent made of human serum albumin nanoparticles (HSA NPs) containing 5-FU for chemo-radiotherapy and decorating LRP-1-targeting peptide for tumor localization, Cy7 fluorophore for diagnostic imaging. The nanoparticle-based theranostic agent accurately targeted the tumor designated by LRP-1 responding radiation and showed dramatically improved therapeutic efficacy in the radio-resistant PDX model. In conclusion, we have identified LRP-1 as a signature protein of radio-resistant CRC and successfully developed LRP-1-targeting HSA-NP containing 5-FU that is a novel theranostic tool for both diagnostic imaging and neoadjuvant therapy of CRC patients. This approach is clinically applicable to improve the effectiveness of neo-adjuvant radiotherapy and increase the ratio of complete tumor response in radio-resistant CRC.

     

    Affiliations

    Kyoung Jin Lee  1 , Eun Jung Ko  2 , Yun-Yong Park  3 , Seok Soon Park  2 , Eun Jin Ju  2 , Jin Park  2 , Seol Hwa Shin  2 , Young-Ah Suh  4 , Seung-Mo Hong  5 , In Ja Park  6 , Kyu-Pyo Kim  7 , Jung Jin Hwang  3 , Se Jin Jang  4 , Jung Shin Lee  7 , Si Yeol Song  8 , Seong-Yun Jeong  9 , Eun Kyung Choi  10
    1 Asan 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 Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, South Korea.
    2 Asan 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.
    3 Asan 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.
    4 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.
    5 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
    6 Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
    7 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
    8 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.
    9 Asan 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. Electronic address: syj@amc.seoul.kr.
    10 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.

  • 키워드
    Colorectal cancer (CRC); Low-density lipoprotein receptor-related protein-1 (LRP-1); Neoadjuvant radiotherapy; Radio-resistant.
  • 덧글달기
    덧글달기
       IP : 52.86.117.142

    등록