Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy.
Theranostics
; 12(3): 1247-1266, 2022.
Article
en En
| MEDLINE
| ID: mdl-35154485
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nanopartículas
/
Técnicas Fotoacústicas
/
Vesículas Extracelulares
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Theranostics
Año:
2022
Tipo del documento:
Article