Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2019; 9(20):5886-5898. doi:10.7150/thno.32416 This issue Cite

Research Paper

Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment

Fang Li1,2*, Yu Wang1*, Wei-liang Chen1*, Dan-dan Wang1, Ye-juan Zhou1, Ben-gang You1, Yang Liu1, Chen-xi Qu1, Shu-di Yang1, Meng-tian Chen1, Xue-nong Zhang1✉

1. Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China
2. Department of Pharmacy, Children` s Hospital of Soochow University, Suzhou 215025, People's Republic of China
*These three authors contributed equally to the paper.

✉ Corresponding author: The Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, DuShuHu High Education Zone, Su Zhou, Jiang Su Province, People's Republic of China, 215123; Tel/Fax: +86 (0512) 65882087; E-mail: zhangxu More

Citation:
Li F, Wang Y, Chen Wl, Wang Dd, Zhou Yj, You Bg, Liu Y, Qu Cx, Yang Sd, Chen Mt, Zhang Xn. Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment. Theranostics 2019; 9(20):5886-5898. doi:10.7150/thno.32416. https://www.thno.org/v09p5886.htm
Other styles

File import instruction

Abstract

Graphic abstract

Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen.

Methods: We designed, for the first time, a rational therapy strategy via intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the in vitro tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model.

Results: The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated in vitro. In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency in vivo. The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy.

Conclusion: Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment.

Keywords: anti-angiogenesis, combined therapy, co-delivery, multi-functional nanoparticles, VEGF siRNA, etoposide

Citation styles

APA
Li, F., Wang, Y., Chen, W.l., Wang, D.d., Zhou, Y.j., You, B.g., Liu, Y., Qu, C.x., Yang, S.d., Chen, M.t., Zhang, X.n. (2019). Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment. Theranostics, 9(20), 5886-5898. https://doi.org/10.7150/thno.32416.

ACS
Li, F.; Wang, Y.; Chen, W.l.; Wang, D.d.; Zhou, Y.j.; You, B.g.; Liu, Y.; Qu, C.x.; Yang, S.d.; Chen, M.t.; Zhang, X.n. Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment. Theranostics 2019, 9 (20), 5886-5898. DOI: 10.7150/thno.32416.

NLM
Li F, Wang Y, Chen Wl, Wang Dd, Zhou Yj, You Bg, Liu Y, Qu Cx, Yang Sd, Chen Mt, Zhang Xn. Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment. Theranostics 2019; 9(20):5886-5898. doi:10.7150/thno.32416. https://www.thno.org/v09p5886.htm

CSE
Li F, Wang Y, Chen Wl, Wang Dd, Zhou Yj, You Bg, Liu Y, Qu Cx, Yang Sd, Chen Mt, Zhang Xn. 2019. Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment. Theranostics. 9(20):5886-5898.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use