한빛사논문
- 조회347
연세대학교
Jeongrae Kim1, Hin Kiu Lee2, Junwon Park3, Seong Ik Jeon4, Il Seong Lee1, Wan Su Yun1, Yujeong Moon1, Jiwoong Choi5, Man Kyu Shim5, Jinseong Kim4, Hanhee Cho4, Nayeon Shim4, Namcheol Hwang6, Gyan Raj Koirala2, Minjun Gwak2, Sangheon Han3, Dong-Hwee Kim1, Won Seok Chang3, Tae-il Kim2, Kwangmeyung Kim4
1KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
2School of Chemical Engineering, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea
3Department of Neurosurgery and Brain Research Institute, College of Medicine, Yonsei University, 50–1 Yonsei-Ro, Seodaemun-gu, Seoul 03722, Republic of Korea
4College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Woman’s University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea
5Biomedical Research Institute, Korea Institute of Science and Technology (KIST), 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea
6Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea
J.K., H.K.L., J.P., and S.Ik.J. contributed equally to this work.
CORRESPONDING AUTHORS: Won Seok Chang, Tae-il Kim, Kwangmeyung Kim
Abstract
Photodynamic therapy shows promise for glioma treatment with powerful efficacy and low resistance, however, its effectiveness is significantly lowered by inadequate light delivery through the skull. Herein, a needle-type implantable microLED device and cathepsin B-responsive prodrug nanoparticles (PNPs) are newly exploited for glioma's chemo-photodynamic combination therapy. The microLED containing four small LEDs on the tip of its guide needle can be implanted into the center of glioma tissues without large area opening of skull, uniformly irradiating light to deep glioma tissues. PNPs are formulated via self-assembly of heterobifunctional prodrug composed of doxorubicin, verteporfin, and cathepsin B-cleavable peptide linker, wherein they stably maintain inactive nanoparticle structures in normal physiological conditions and specifically deliver therapeutic age to cathepsin B-overexpressed glioma tissues. In vitro cellular assays, PNPs irradiated with showed the synergistic cytotoxicity of DOX and VFP only in cathepsin B-overexpressed cancer cells rather than normal cells. In tumor-bearing mice, PNPs showed high tumor accumulation via the nanoparticle-driven enhanced permeation and retention (EPR) effect and they also exhibited remarkable therapeutic efficacy against glioma under microLED-mediated light irradiation via chemo-photodynamic combination therapy. Accordingly, applying microLED with PNPs is an outstanding strategy to defeat glioma with cooperative chemo-photodynamic effects, minimal invasiveness, and desirable systemic/local safety.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-07-17)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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