경북대, 한국생명공학연구원 / 박용대, 전종호*, 박성환*
Abstract
Dual-modular imaging approaches combining near-infrared (NIR) fluorescence (FLI) and photoacoustic imaging (PAI) require suitable contrast agents to produce dual-modular signals. Although nanoparticles have been used to develop PAI agents, small molecule-based imaging agents have not been extensively studied, highlighting the need to design new fluorophores with an enhanced multifunctional ability. Thus, in this study, we designed a novel squaraine (SQ)-based dye and reported its rational preparation and conjugation with a cancer targeting peptide. Specifically, benzoindole-derived SQ (BSQ) showed strong absorption and fluorescence properties at above 650 nm under aqueous conditions, with a maximum absorption and emission at 665 and 680 nm, respectively. Moreover, PA signal scanning experiments revealed a maximum signal intensity in the range 680-700 nm. BSQ was also conjugated with cyclic arginine-glycine-aspartic acid (cRGD) to improve its active targeting ability for the αvβ3 integrin, which is overexpressed in various cancer and angiogenic cells. A series of in vitro, in vivo, and ex vivo FLI studies showed that the cRGD conjugated BSQ (BSQ-RGD2) successfully stained and targeted αvβ3 integrin-overexpressing tumor cells and xenografts, which were clearly visualized by FLI and PAI. Therefore, BSQ-RGD2 can successfully be applied to dual-modular imaging of the specific biomarker in living animals.
Affiliations
Yong Dae Park 1 , Jam-Eon Park 2 , Hyeon Sik Kim 3 , Seung-Hyeon Choi 2 , Jung Eun Park 4 , Jongho Jeon 4 , Seung-Hwan Park 2
1 Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
2 Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea.
3 Medical Photonics Research Center, Korea Photonics Technology Institute, Gwang-ju 61007, Republic of Korea.
4 Department of Applied Chemistry, School of Applied Chemical Engineering, Kyungpook National University, Daegu 41566, Republic of Korea.
편집위원
최근 분자영상 연구는 하나가 아닌 다중모드 영상으로 서로의 단점을 보완하고 정확도를 높이는 결과를 보여주고 있다. 이 연구에서는 형광시그널을 보여주는 benzoindole-derived squaraine(BSQ) 염료를 종양표적 펩타이드(cRGD)에 결합하여 근적외선 형광 영상(NIR)과 더불어 광 음향 영상(PAI)이 동시에 가능한 이중 분자영상추적자를 개발하였고, 이를 이용하여 소동물에서 종양의 다중영상까지 보여주는 결과를 제시하고 있다.
2021-01-05 16:59:26