Photoacoustic imaging-guided therapy using dual pH/ultrasound-responsive extracellular vesicle-based nanosonosensitizers

Abstract

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. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.