Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy
- Authors
- Cao, T.G.N.; Kang, Ji Hee; Kim, Wangyu; Lim, Junha; Kang, Su Jin; You, Jae Young; Hoang, Q.T.; Kim, Won Jong; Rhee, Won Jong; Kim, Chulhong; Ko, Young Tag; Shim, Min Suk
- Issue Date
- Jan-2022
- Publisher
- Ivyspring International Publisher
- Keywords
- Extracellular vesicle; PH-sensitive release; Photoacoustic imaging; Sonodynamic cancer therapy; Sonotheranostics
- Citation
- Theranostics, v.12, no.3, pp.1247 - 1266
- Journal Title
- Theranostics
- Volume
- 12
- Number
- 3
- Start Page
- 1247
- End Page
- 1266
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/83327
- DOI
- 10.7150/thno.65516
- ISSN
- 1838-7640
- Abstract
- Sonodynamic therapy has shown promise as an effective alternative to conventional photodynamic therapy owing to its ability to treat deep-seated tumors. However, the development of stimuli-responsive sonosensitizers with high biocompatibility faces a significant challenge. Methods: In this study, we developed dual stimuli-responsive sonosensitizers with desirable biosafety using extracellular vesicles (EVs), a class of naturally occurring nanoparticles. Indocyanine green (ICG), which functions as both a sonosensitizer and photoacoustic (PA) imaging agent, was loaded into EVs, together with paclitaxel (PTX) and sodium bicarbonate (SBC), to achieve pH-responsive PA imaging-guided chemo-sonodynamic combination therapy. Results: The EVs significantly improved the cellular uptake of ICG, thus triggering enhanced sonodynamic effects in breast cancer cells. SBC-, ICG-, and PTX-loaded EV [SBC-EV(ICG/PTX)] efficiently released the PTX in response to acidic pH in the endo/lysosomes because CO2 bubbles generated from the SBC caused the EV membranes to burst. The drug release was further facilitated by ultrasound (US) treatment, demonstrating dual pH/US-responsive drug release. The ICG- and PTX-loaded EVs exhibited efficient anticancer activity against breast tumor cells owing to the combination of chemo-sonodynamic therapy. High-resolution PA imaging visualized the preferential tumor accumulation of SBC-EV(ICG/PTX) in tumor-bearing mice. Notably, a single intravenous injection of SBC-EV(ICG/PTX) with US irradiation significantly suppressed tumor growth in mice without systemic toxicity. Conclusions: Our findings demonstrate that dual stimuli-responsive SBC-EV(ICG/PTX) are promising sonotheranostic nanoplatforms for safe and efficient chemo-sonodynamic combination cancer therapy and photoacoustic imaging. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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