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Biomaterials, May 25 2024, 310 S0142-9612(24)00167-4 | https://doi.org/10.1016/j.biomaterials.2024.122633 Noninvasive ROS imaging and drug delivery monitoring in the tumor microenvironment

Wonsik Jung ^a,b,1, Muhammad Asaduddin ^c,1, Dohyun Yoo ^a,b, Dong Yun Lee ^d, Youngju Son ^a,b, Dohyeon Kim ^a,b, Hyeongseop Keum ^a,b, Jungun Lee ^a,b, Sung-Hong Park^c, Sangyong Jon ^a,b

^aDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea

^bCenter for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea

^cDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea

^dDepartment of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Seoul, 05505, Republic of Korea

¹These authors contributed equally to this work.

Corresponding authors : Sung-Hong Park, Sangyong Jon

Abstract

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn ²⁺)-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn ²⁺, which induces T1-weighted MRI signal enhancement. Mn@BRNPs show more rapid and greater MRI signal enhancement in high ROS-producing A549 lung carcinoma cells compared with low ROS-producing DU145 prostate cancer cells. A pseudo three-compartment model devised for the ROS-reactive MRI probe enables mapping of the distribution and concentration of ROS within the tumor. Furthermore, doxorubicin-loaded, cancer-targeting ligand biotin-conjugated Dox/Mn@bt-BRNPs show considerable accumulation in A549 tumors and also effectively inhibit tumor growth without causing body weight loss, suggesting their usefulness as a new theranostic agent. Collectively, these findings suggest that Mn@bt-BRNPs could be used as an imaging probe capable of detecting ROS levels and monitoring drug delivery in the TME with potential applicability to other inflammatory diseases.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-31)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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