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Theranostics 2019; 9(4):1047-1065. doi:10.7150/thno.29820 This issue Cite

Research Paper

GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer

Hui Huang, Yang Dong, Yanhua Zhang, Dan Ru, Zhihua Wu, Jiali Zhang, Ming Shen, Yourong Duan✉, Ying Sun✉

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.

✉ Corresponding authors: yrduanorg; ysunorg

Citation:
Huang H, Dong Y, Zhang Y, Ru D, Wu Z, Zhang J, Shen M, Duan Y, Sun Y. GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer. Theranostics 2019; 9(4):1047-1065. doi:10.7150/thno.29820. https://www.thno.org/v09p1047.htm
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Abstract

Graphic abstract

Background: Platinum (II) (Pt(II))-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient's quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. Multifunctional tumor-targeted nanosized ultrasound contrast agents (glutathione (GSH)-sensitive platinum (IV) (Pt(IV)) prodrug-loaded phase-transitional nanoparticles, Pt(IV) NP-cRGD) were developed for precise theranostics against ovarian cancer.

Methods: Pt(IV) NP-cRGD were composed of a perfluorohexane (PFH) liquid core, a hybrid lipid-polymer shell with PLGA12k-PEG2k and DSPE-PEG1k-Pt(IV), and an active targeting ligand, the cRGD peptide (PLGA: poly(lactic-co-glycolic acid), PEG: polyethylene glycol, DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cRGD: cyclic Arg-Gly-Asp). Pt(IV), a popular alternative to Pt(II), was covalently attached to DSPE-PEG1k to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. The potential of Pt(IV) NP-cRGD as contrast agents for ultrasound (US) imaging was assessed in vitro and in vivo. Moreover, studies on the antitumor efficiency and antitumor mechanism of Pt(IV) NP-cRGD assisted by US were carried out.

Results: Pt(IV) NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and US-triggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt(IV) NP-cRGD with US consumed GSH and enhanced reactive oxy gen species (ROS) levels, which further causes mitochondria-mediated apoptosis.

Conclusion: A multifunctional nanoplatform based on phase-transitional Pt(IV) NP-cRGD with US exhibited excellent echogenic signals, brilliant therapeutic efficacy and limited side effect, suggesting precise theranostics against ovarian cancer.

Keywords: platinum (IV), phase transition, ultrasound contrast agents, mitochondrial apoptosis, ovarian cancer.

Citation styles

APA
Huang, H., Dong, Y., Zhang, Y., Ru, D., Wu, Z., Zhang, J., Shen, M., Duan, Y., Sun, Y. (2019). GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer. Theranostics, 9(4), 1047-1065. https://doi.org/10.7150/thno.29820.

ACS
Huang, H.; Dong, Y.; Zhang, Y.; Ru, D.; Wu, Z.; Zhang, J.; Shen, M.; Duan, Y.; Sun, Y. GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer. Theranostics 2019, 9 (4), 1047-1065. DOI: 10.7150/thno.29820.

NLM
Huang H, Dong Y, Zhang Y, Ru D, Wu Z, Zhang J, Shen M, Duan Y, Sun Y. GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer. Theranostics 2019; 9(4):1047-1065. doi:10.7150/thno.29820. https://www.thno.org/v09p1047.htm

CSE
Huang H, Dong Y, Zhang Y, Ru D, Wu Z, Zhang J, Shen M, Duan Y, Sun Y. 2019. GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer. Theranostics. 9(4):1047-1065.

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