KEYWORDS: Tumors, In vivo imaging, Cancer, Photoacoustic spectroscopy, In vitro testing, Pulsed laser operation, Photodynamic therapy, Optical parametric oscillators, Indocyanine green, Breast cancer
Recently, sonodynamic therapy (SDT) is actively developed, and the reason is that it goes beyond the conventional photodynamic therapy (PDT). SDT demonstrates exceptional ability to treat deep-seated tumor. However, it is difficult to develop sonosensitizers used in SDT. Herein, we demonstrate dual stimuli-responsive theranostic nanosonosensitizers using biocompatible extracellular vesicles (EVs), a class of naturally occurring nanoparticles. With this nanosonosensitizers, we can achieve both high-cancer-targeting and biocompatible properties. Indocyanine green (ICG), used as an sonosensitizer and a photoacoustic (PA) imaging agent, was loaded into EV with paclitaxel (PTX) and sodium bicarbonate (SBC) to achieve pH-responsive PA image-guided chemo-SDT. The SBC trapped in the EV generates CO2 bubbles and causes the EV to burst. That's why SBC-, ICG-, PTX-equipped EVs [ICG/PTX] can efficiently release drugs in response to acidic pH in the endo/lysosomes. The photostability and cellular uptake of ICG was improved by EVs. Further, the ICG-, PTX-loaded EVs and SBCEV( ICG/PTX) showed great anticancer activities against breast cancer cells. The effect of SBC-EV was shown through high resolution PA imaging, which showed that the SBC-EV is accumulated in tumor. SBC-EV (ICG/PTX) with insonification showed that inhibition of tumor growth is possible without toxicity. Thus, this study demonstrates that dual stimuli-responsive SBC-EV(ICG/PTX) holds a great potential for clinical translation of chemo-sonodynamic cancer theranostics.
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