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Theranostics 2022; 12(3):1247-1266. doi:10.7150/thno.65516 This issue Cite

Research Paper

Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy

Thuy Giang Nguyen Cao1*, Ji Hee Kang2*, Wangyu Kim3*, Junha Lim4*, Su Jin Kang1, Jae Young You1, Quan Truong Hoang1, Won Jong Kim4, Won Jong Rhee1,5✉, Chulhong Kim3✉, Young Tag Ko2✉, Min Suk Shim1✉

1. Division of Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
2. College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.
3. Department of Electrical Engineering, Convergence IT Engineering, and Mechanical Engineering, Medical Device Innovation Center, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
4. Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
5. Research Center for Bio Materials & Process Development, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea.
*These authors contributed equally to this work.

✉ Corresponding authors: Dr. Won Jong Rhee, Tel: +82-32-835-8299; E-mail address: wjrheeac.kr; Dr. Chulhong Kim, Tel: +82-54-279-8805; E-mail address: chulhongedu; Dr. Young Tag Ko, Tel: +82-32-820-4923; E-mail address: youngtakkoac.kr; Dr. Min Suk Shim, Tel: +82-32-835-8268; E-mail address: msshimac.kr. More

Citation:
Nguyen Cao TG, Kang JH, Kim W, Lim J, Kang SJ, You JY, Truong Hoang Q, Kim WJ, Rhee WJ, Kim C, Ko YT, Shim MS. Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics 2022; 12(3):1247-1266. doi:10.7150/thno.65516. https://www.thno.org/v12p1247.htm
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Abstract

Graphic 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.

Keywords: extracellular vesicle, sonodynamic cancer therapy, sonotheranostics, pH-sensitive release, photoacoustic imaging

Citation styles

APA
Nguyen Cao, T.G., Kang, J.H., Kim, W., Lim, J., Kang, S.J., You, J.Y., Truong Hoang, Q., Kim, W.J., Rhee, W.J., Kim, C., Ko, Y.T., Shim, M.S. (2022). Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics, 12(3), 1247-1266. https://doi.org/10.7150/thno.65516.

ACS
Nguyen Cao, T.G.; Kang, J.H.; Kim, W.; Lim, J.; Kang, S.J.; You, J.Y.; Truong Hoang, Q.; Kim, W.J.; Rhee, W.J.; Kim, C.; Ko, Y.T.; Shim, M.S. Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics 2022, 12 (3), 1247-1266. DOI: 10.7150/thno.65516.

NLM
Nguyen Cao TG, Kang JH, Kim W, Lim J, Kang SJ, You JY, Truong Hoang Q, Kim WJ, Rhee WJ, Kim C, Ko YT, Shim MS. Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics 2022; 12(3):1247-1266. doi:10.7150/thno.65516. https://www.thno.org/v12p1247.htm

CSE
Nguyen Cao TG, Kang JH, Kim W, Lim J, Kang SJ, You JY, Truong Hoang Q, Kim WJ, Rhee WJ, Kim C, Ko YT, Shim MS. 2022. Engineered extracellular vesicle-based sonotheranostics for dual stimuli-sensitive drug release and photoacoustic imaging-guided chemo-sonodynamic cancer therapy. Theranostics. 12(3):1247-1266.

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