Renal Clearable Ru-based Coordination Polymer Nanodots for Photoacoustic Imaging Guided Cancer Therapy

Rui Zhang, Xing Fan, Zhouqi Meng, Haiping Lin, Qiutong Jin, Fei Gong, Ziliang Dong, Youyong Li, Qian Chen, Zhuang Liu, Liang Cheng^✉

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.

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Citation:
Zhang R, Fan X, Meng Z, Lin H, Jin Q, Gong F, Dong Z, Li Y, Chen Q, Liu Z, Cheng L. Renal Clearable Ru-based Coordination Polymer Nanodots for Photoacoustic Imaging Guided Cancer Therapy. Theranostics 2019; 9(26):8266-8276. doi:10.7150/thno.36986. Available from http://www.thno.org/v09p8266.htm

Abstract

Rationale: Despite the promises of applying theranostic nanoagents for imaging-guided cancer therapy, the chronic retention of these nanoagents may cause safety concerns that hinder their future clinical applications. The metabolizable nanoagents with rapid renal excretion to avoid long-term toxicity is a possible solution for this issue.

Method: Herein, we synthesize ultra-small metal-organic coordination polymer nanodots based on ruthenium ion (Ru³⁺) / phenanthroline (Phen) (Ru-Phen CPNs) with superior near-infrared (NIR) absorption. The size, photothermal conversion, cytotoxicity, photoacoustic imaging, in vivo & in vitro cancer treatment efficiency and biosafety are tested.

Results: The size of the ultra-small Ru-Phen CPNs is 6.5 nm. The photothermal conversion efficiency is measured to be ~ 60.69 %, much higher than that of previously reported photothermal agents. The Ru-Phen CPNs could be employed for photoacoustic (PA, 808 nm) imaging-guided photothermal therapy (PTT, 808 nm, 0.5 W/cm²) with great performance. Notably, the intrinsic PA signals (808 nm) of Ru-Phen CPNs are observed in kidneys of treated mice, illustrating efficient renal clearance of those ultra-small CPNs. Moreover, the clearance of CPNs is further confirmed by detecting Ru levels in urine and feces.

Conclusion: Our work presents a new type of ultra-small Ru-based CPNs with a record high photothermal conversion efficiency, efficient tumor retention after systemic administration, and rapid renal excretion to avoid long-term toxicity, promising for imaging-guided photothermal therapy.

Keywords: Ru-Phen CPNs, ultra-small size nanodots, photoacoustic imaging, photothermal therapy, renal clearance