Exosome membrane-sheathed and multi-stimuli-responsive MnO2 nanoparticles with self-oxygenation and energy depletion abilities potentiate the sonodynamic therapy of hypoxic tumors

被引：19

作者：

Hoang, Quan Truong ^{[1
]}

Cao, Thuy Giang Nguyen ^{[1
]}

Kang, Su Jin ^{[1
]}

Lee, Minjong ^{[2
,3
]}

Kang, Ji Hee ^{[4
]}

Park, Hyun Su ^{[5
]}

Kim, Jong-Eun ^{[6
]}

Bhang, Suk Ho ^{[5
]}

Ko, Young Tag ^{[4
]}

Rhee, Won Jong ^{[1
,7
]}

Shim, Min Suk ^{[1
]}

机构：

[1] Incheon Natl Univ, Div Bioengn, Incheon 22012, South Korea

[2] Ewha Womans Univ, Coll Med, Dept Internal Med, Seoul 07804, South Korea

[3] Ewha Womans Univ, Med Ctr, Dept Internal Med, Seoul 07804, South Korea

[4] Gachon Univ, Coll Pharm, Incheon 21936, South Korea

[5] Sungkyunkwan Univ, Sch Chem Engn, Suwon 16419, South Korea

[6] Yonsei Univ, Coll Dent, Dept Prosthodont, Seoul 03722, South Korea

[7] Incheon Natl Univ, Res Ctr Bio Mat & Proc Dev, 119 Acad Ro, Incheon 22012, South Korea

来源：

CHEMICAL ENGINEERING JOURNAL | 2023年 / 472卷

基金：

新加坡国家研究基金会;

关键词：

Sonodynamic therapy; Hollow MnO 2; Exosome membrane; Glycolysis inhibition; Hypoxia; LACTATE-DEHYDROGENASE; CANCER; INHIBITION;

D O I：

10.1016/j.cej.2023.144871

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Sonodynamic therapy (SDT), which employs ultrasound (US) to activate sonosensitizers to generate reactive oxygen species (ROS), has emerged as an effective approach for treating deep-seated tumors. However, poor biocompatibility of sonosensitizers and hypoxic tumor microenvironments are significant challenges for in vivo SDT. Herein, hollow manganese dioxide nanoparticles (MnO2 NPs) encapsulating the sonosensitizer, indocyanine green (ICG), were developed for enhanced sonodynamic cancer therapy by high ICG loading and tumor hypoxia relief. A glycolysis inhibitor, FX11, was co-loaded into MnO2 NPs to boost SDT efficacy via FX11-induced energy depletion. Because of the high biocompatibility, low immunogenicity, and efficient intracellular delivery of exosomes, ICG- and FX11-loaded MnO2 NP [M(ICG/FX11)] was coated with exosome membranes for safe and efficient in vivo SDT. The exosome membrane-coated M(ICG/FX11) [Exo-M(ICG/FX11)] exhibited triple pH/ H2O2/US-responsive drug release while avoiding premature drug leakage. Exo-M(ICG/FX11) was efficiently internalized by MCF-7 human breast cancer cells and catalyzed the endogenous H2O2 to generate O2 to relieve tumor hypoxia. Consequently, Exo-M(ICG/FX11) markedly boosted intracellular ROS levels upon US irradiation. Moreover, Exo-M(ICG/FX11) effectively inhibited glycolytic pathways, thereby potentiating the anticancer efficacy of SDT. An in vivo study using tumor-xenografted mice demonstrated that Exo-M(ICG/FX11) effectively accumulated in tumors and alleviated tumor hypoxia. Notably, Exo-M(ICG/FX11) combined with US substantially suppressed tumors in mice without causing systemic toxicity, owing to the synergistic effect of O2 suppliedSDT and energy-depleting chemotherapy. This study demonstrates that biomimetic Exo-M(ICG/FX11) is a safe and efficient nanoplatform for the treatment of hypoxic tumors.

引用

页数：13