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Perfluorocarbon nanodroplets stabilized with cisplatin-prodrug-constructed lipids enable efficient tumor oxygenation and chemo-radiotherapy of cancer

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Abstract

Concurrent chemo-radiotherapy has been widely applied for the treatment of a wide range of cancers, but its therapeutic efficacy against most solid tumors is severely impaired by their intrinsic hypoxic microenvironments. Utilizing the high oxygen loading capacity of perfluoro-15-crown-5-ether (PFCE), herein, we prepare PFCE nanodroplets with cisplatin prodrug (cisPt(IV)) conjugated phospholipids and other commercial lipids as the stabilizer to enable tumor targeted oxygen shuttling. The obtained PFCE@cisPt(IV)-Lip shows high physiological stability and efficient oxygen loading capacity. As vividly visualized under an in vivo photoacoustic imaging system, tumors on the mice with intravenous injection of such PFCE@cisPt(IV)-Lip show effective tumor oxygenation. Together with X-ray exposure, such PFCE@cisPt(IV)-Lip upon intravenous injection could induce severe DNA damage of cells, thereby remarkably suppressing the tumor growth and significantly prolonging their survival time without causing obvious toxic side effects. This work highlights PFCE@cisPt(IV)-Lip as an adjuvant nanomedicine for enhanced chemo-radiotherapy of tumors by attenuating hostile tumor hypoxia, indicating its promising potential for future clinical translation ascribed to its straightforward synthesis and notable tumor growth inhibition at a safe dose.

Graphical abstract: Perfluorocarbon nanodroplets stabilized with cisplatin-prodrug-constructed lipids enable efficient tumor oxygenation and chemo-radiotherapy of cancer

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Supplementary files

Article information


Submitted
20 Feb 2020
Accepted
12 Jun 2020
First published
12 Jun 2020

Nanoscale, 2020, Advance Article
Article type
Paper

Perfluorocarbon nanodroplets stabilized with cisplatin-prodrug-constructed lipids enable efficient tumor oxygenation and chemo-radiotherapy of cancer

L. Yao, L. Feng, D. Tao, H. Tao, X. Zhong, C. Liang, Y. Zhu, B. Hu, Z. Liu and Y. Zheng, Nanoscale, 2020, Advance Article , DOI: 10.1039/D0NR01476A

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