Theranostics 2019; 9(2):526-536. doi:10.7150/thno.30779 This issue Cite

Research Paper

Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging

Zhen Yang1,2,4*, Jibin Song3*, Wei Tang4*, Wenpei Fan4, Yunlu Dai4, Zheyu Shen4, Lisen Lin4, Siyuan Cheng4, Yijing Liu4, Gang Niu4, Pengfei Rong1,2, Wei Wang1,2✉, Xiaoyuan Chen4✉

1. Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
2. Engineering and Technology Research Center for Xenotransplantation of Human Province, Changsha, Hunan, China.
3. MOE Key Laboratory for Analytical Science of Food Safety and Biology College of Chemistry, Fuzhou University, Fuzhou 350108, China
4. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) Bethesda, Maryland 20892, United States
*Z. Yang, J. Song and W. Tang contributed equally to this work

Citation:
Yang Z, Song J, Tang W, Fan W, Dai Y, Shen Z, Lin L, Cheng S, Liu Y, Niu G, Rong P, Wang W, Chen X. Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging. Theranostics 2019; 9(2):526-536. doi:10.7150/thno.30779. https://www.thno.org/v09p0526.htm
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Abstract

Graphic abstract

Molecular photoacoustic imaging (PA) is a promising technology to understand tumor pathology and guide precision therapeutics. Despite the capability of activatable PA probes to image tumor-specific biomarkers, limitations in their molecular structure hamper them from effective drug delivery and the drug release monitoring. Herein, we developed a perylene diimide (PDI) based theranostic platform that provides noninvasive PA imaging signals to monitor tumor-specific pH-responsive drug release.

Methods: we first designed and synthesized an acid-responsive amine-substituted PDI derivative. The pH sensitive properties of the PDI was demonstrated by density functional theory (DFT) calculations, UV-vis experiments and PA studies. The theranostic platform (THPDINs) was fabricated by self-assembly of the acid-responsive PDI, a pH irrelevant IR825 dye, and anti-cancer drug doxorubicin (DOX). The PA properties in various pH environment, drug delivery, cytotoxicity, cell uptake, ratiometric PA imaging and anti-tumor efficacy of the THPDINs were investigated in vitro and in vivo by using U87MG glioma cell line and U87MG tumor model.

Results: We found that our designed PDI was sensitive to the tumor specific pH environment, reflected by absorbance shift, PA intensity and aggregation morphology changes in aqueous solution. The as-synthesized pH sensitive PDI acted as a molecular switch in the THPDINs, in which the switch can be triggered in the mild acidic tumor microenvironment to accelerate DOX release. Meanwhile, the DOX release could be monitored by ratiometric PA imaging.

Conclusions: We developed a multifunctional PDI based theranostic platform for noninvasive real-time ratiometric PA imaging of tumor acidic pH and monitoring of drug release in living mice simultaneously. This strategy will shed light on the development of smart activatable theranostic nanoplatforms and will significantly advance the application of PA theranostics in biology and medicine.

Keywords: photoacoustic imaging, ratiometric imaging, drug delivery, pH-responsive, theranostics


Citation styles

APA
Yang, Z., Song, J., Tang, W., Fan, W., Dai, Y., Shen, Z., Lin, L., Cheng, S., Liu, Y., Niu, G., Rong, P., Wang, W., Chen, X. (2019). Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging. Theranostics, 9(2), 526-536. https://doi.org/10.7150/thno.30779.

ACS
Yang, Z.; Song, J.; Tang, W.; Fan, W.; Dai, Y.; Shen, Z.; Lin, L.; Cheng, S.; Liu, Y.; Niu, G.; Rong, P.; Wang, W.; Chen, X. Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging. Theranostics 2019, 9 (2), 526-536. DOI: 10.7150/thno.30779.

NLM
Yang Z, Song J, Tang W, Fan W, Dai Y, Shen Z, Lin L, Cheng S, Liu Y, Niu G, Rong P, Wang W, Chen X. Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging. Theranostics 2019; 9(2):526-536. doi:10.7150/thno.30779. https://www.thno.org/v09p0526.htm

CSE
Yang Z, Song J, Tang W, Fan W, Dai Y, Shen Z, Lin L, Cheng S, Liu Y, Niu G, Rong P, Wang W, Chen X. 2019. Stimuli-Responsive Nanotheranostics for Real-Time Monitoring Drug Release by Photoacoustic Imaging. Theranostics. 9(2):526-536.

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