2025년 7월 10일
Engineered Cell-Derived Nanovesicles with CAR and PH20 for Enhanced Targeted Photodynamic Cancer Therapy and Tumor Microenvironment Modulation
Abstract
Photodynamic therapy (PDT) is a promising cancer treatment, but its clinical use is limited by nontargeted photosensitizers (PS) that accumulate in normal tissues, causing adverse effects, and poor penetration in tumor tissues due to the dense extracellular matrix (ECM). Here an innovative approach is presented using cell-derived nanovesicles (CNVs) engineered with chimeric antigen receptor (CAR) and hyaluronidase PH20 to enhance targeted PDT. The CAR–PH20 CNVs, loaded with the photosensitizer pheophorbide a (PheoA), specifically target HER2-expressing tumor cells and degrade hyaluronic acid in the tumor microenvironment (TME), improving tumor penetration and drug distribution. In vitro and in vivo experiments demonstrate increased reactive oxygen species (ROS) generation, improved tumor retention, and enhanced therapeutic efficacy compared to conventional methods. When combined with laser irradiation, these CNVs induce significant tumor cell apoptosis and inhibit tumor growth in mouse models, while minimizing toxicity to normal tissues. This platform offers a promising strategy for targeted, TME-modulating PDT with improved efficacy, and reduced side effects, marking a significant advance in nanodrug-based cancer therapies.
- 형식: Research article
- 게재일: 2025년 06월(BRIC 등록일 2025-06-26)
- 연구진: 국내 연구진
- 분야: 바이오·의료융합>바이오소재
Authors and Affiliations
Hyeon-Ji Oh1, Gwang Yeol Park2, Jieun Han1, Boram Son2,3, Jun-Hyeok Han1, Hyomin Choi2, Chun Gwon Park4, Dong Wook Choi5, Sung-Soo Park6, Wooram Park1,7, Hee Ho Park2,5,8
1Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419 Republic of Korea
2Department of Bioengineering, College of Engineering, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul, 04763 Republic of Korea
3Department of Bio and Fermentation Convergence Technology, Kookmin University, 77, Jeongneung-ro, Seongbuk-gu, Seoul, 02707 Republic of Korea
4Department of Biomedical Engineering, Institute for Cross-disciplinary Studies (ICS), SKKU, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419 Republic of Korea
5Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841 Republic of Korea
6Biodrone Research Institute, Mdimune Inc., 49, Achasan-ro, Seongdong-gu, Seoul, 04790 Republic of Korea
7Department of MetaBioHealth, ICS, SKKU, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419 Republic of Korea
8SIMPLE Planet Inc., 48, Achasan-ro 17-gil, Seongdong-gu, Seoul, 04799 Republic of Korea
H.-J.O. and G.Y.P. contributed equally to this work
Corresponding Authors: Wooram Park, Hee Ho Park
관련 인터뷰
최근 고형암 치료를 위하여, CAR-T 등 면역세포치료제가 주목받고 있습니다. 그러나, 살아있는 면역세포를 이용한 치료는 고형암의 면역억제적 미세환경 (TME, tumor microenvironment)에 의해 쉽게 제어되며, 그 적용이 제한되고 있습니다. 이를 해결하기 위한 방법들이 연구되고 있으나, 저희는 살아있는 세포가 아닌 세포 유래의 나노베지클 (CNVs, cell-derived nanovesicles)을 이용한 약물전달시스템을 이용하여 이런 제한을 극복하고자 하였습니다.