Quan Truong Hoang (인천대학교) | 한빛사논문 > 한빛사

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조회514

인천대학교

Biomaterials, Available online 11 July 2023 | https://doi.org/10.1016/j.biomaterials.2023.122242 Bioreducible exosomes encapsulating glycolysis inhibitors potentiate mitochondria-targeted sonodynamic cancer therapy via cancer-targeted drug release and cellular energy depletion

Thuy Giang Nguyen Cao^a,1, Quan Truong Hoang ^a,1, Ji Hee Kang ^b,1, Su Jin Kang ^a,1, Vasanthan Ravichandran ^a, Won Jong Rhee ^a,c, Minjong Lee ^d,e, Young Tag Ko ^b, Min Suk Shim ^a

^aDivision of Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea
^bCollege of Pharmacy, Gachon University, Incheon, 21936, Republic of Korea
^cResearch Center for Bio Materials & Process Development, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon, 22012, Republic of Korea
^dDepartment of Internal Medicine, Ewha Womans University College of Medicine, Seoul, 07804, Republic of Korea
^eDepartment of Internal Medicine, Ewha Womans University Medical Center, Seoul, 07804, Republic of Korea

¹These authors contributed equally to this work.
Corresponding authors: Won Jong Rhee, Minjong Lee, Young Tag Ko, Min Suk Shim

Abstract

Nanocarrier-assisted sonodynamic therapy (SDT) has shown great potential for the effective and targeted treatment of deep-seated tumors by overcoming the critical limitations of sonosensitizers. However, in vivo SDT using nanocarriers is still constrained by their intrinsic toxicity and nonspecific cargo release. In this study, we developed bioreducible exosomes for the safe and tumor-specific delivery of mitochondria-targeting sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (T-Ce6)] and glycolysis inhibitors (FX11). Redox-cleavable diselenide linker-bearing lipids were embedded into exosomes to trigger drug release in response to overexpressed glutathione in the tumor microenvironment. Bioreducible exosomes facilitate the cytoplasmic release of their payload in the reducing environment of tumor cells. They significantly enhance drug release and sonodynamic effects when irradiated with ultrasound (US). The mitochondria-targeted accumulation of T-Ce6 efficiently damaged the mitochondria of the cells under US irradiation, accelerating apoptotic cell death. FX11 substantially inhibited cellular energy metabolism, potentiating the antitumor efficacy of mitochondria-targeted SDT. Bioreducible exosomes effectively suppressed tumor growth in mice without significant systemic toxicity, via a combination of mitochondria-targeted SDT and energy metabolism-targeted therapy. This study offers new insights into the use of dual stimuli-responsive exosomes encapsulating sonosensitizers for safe and targeted sonodynamic cancer therapy.

논문정보

형식Research article
게재일2023년 07월 (BRIC 등록일 2023-08-03)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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