한빛사논문
- 조회1,563
Rae Hyung Kang,‡a Jeong-Eun Jang,‡b Eugene Huh,‡cd Seong Jae Kang,b Dae-Ro Ahn,be Jae Seung Kang,fg Michael J. Sailor,h Seung Geun Yeo,*i Myung Sook Oh,*dj Dokyoung Kim*aklm and Hyo Young Kim*bn
a Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
b Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
c Department of Medical Science of Meridian, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
d Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
e Department of Biological Chemistry, Korea University of Science and Technology, KIST campus, Seoul 02792, Republic of Korea
f Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University, College of Medicine, Seoul 03080, Republic of Korea
g Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea
h Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
i Department of Otorhinolaryngology, Head & Neck Surgery, Kyung Hee University, Seoul 02447, Republic of Korea.
j Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
k Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
l Center for Converging Humanities, Kyung Hee University, Seoul 02447, Republic of Korea
m Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
n R&D Division of Drug Discovery Department, SPARK Biopharma, Seoul 08791, Republic of Korea.
‡ These authors contributed equally to this work.
*Corresponding author
Abstract
Organ-specific cell-penetrating peptides (CPPs) are a class of molecules that can be highly effective at delivering therapeutic cargoes, and they are currently of great interest in cancer treatment strategies. Herein, we describe a new CPP (amino acid sequence serine-isoleucine-tyrosine-valine, or SIWV) that homes to glioblastoma multiforme (GBM) brain tumor tissues with remarkable specificity in vitro and in vivo. The SIWV sequence was identified from an isoform of annexin-A3 (AA3H), a membrane-interacting human protein. The mechanism of intracellular permeation is proposed to follow a caveolin-mediated endocytotic pathway, based on in vitro and in vivo receptor inhibition and genetic knockdown studies. Feasibility as a targeting agent for therapeutics is demonstrated in a GBM xenograft mouse model, where porous silicon nanoparticles (pSiNPs) containing the clinically relevant anticancer drug SN-38 are grafted with SIWV via a poly-(ethylene glycol) (PEG) linker. The formulation shows enhanced in vivo targeting ability relative to a formulation employing a scrambled control peptide, and significant (P < 0.05) therapeutic efficacy relative to free SN-38 in the GBM xenograft animal model.
논문정보
- Research article
- 2020년 08월 (BRIC 등록일 2021-01-04)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
