A novel nanoparticle-based theranostic agent targeting LRP-1 enhances the efficacy of neoadjuvant radiotherapy in colorectal cancer.

Jun 8, 2020

Contributor: Kyoung Jin Lee,Eun Jung Ko,Yun-Yong Park,Seok Soon Park,Eun Jin Ju,Jin Park,Seol Hwa Shin,Young-Ah Suh,Seung-Mo Hong,In Ja Park,Kyu-Pyo Kim,Jung Jin Hwang,Se Jin Jang,Jung Shin Lee,Si Yeol Song,Seong-Yun Jeong,Eun Kyung Choi

A novel nanoparticle-based theranostic agent targeting LRP-1 enhances the efficacy of neoadjuvant radiotherapy in colorectal cancer.

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.
Copyright © 2020. Published by Elsevier Ltd.

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About The Expert

Kyoung Jin Lee

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.

Eun Jung Ko

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.

Yun-Yong Park

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.

Seok Soon Park

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.

Eun Jin Ju

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.

Jin Park

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.

Seol Hwa Shin

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.

Young-Ah Suh

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.

Seung-Mo Hong

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.

In Ja Park

Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.

Kyu-Pyo Kim

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.

Jung Jin Hwang

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.

Se Jin Jang

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.

Jung Shin Lee

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea.

Si Yeol Song

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.

Seong-Yun Jeong

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.

Eun Kyung Choi

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.

References

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