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Theranostics 2019; 9(10):2984-2998. doi:10.7150/thno.31157 This issue Cite

Research Paper

A TRAIL-Delivered Lipoprotein-Bioinspired Nanovector Engineering Stem Cell-Based Platform for Inhibition of Lung Metastasis of Melanoma

Kerong Chen^1*, Xiaoqing Cao^2,3*, Min Li¹, Yujie Su¹, Huipeng Li¹, Mengying Xie¹, Ziqi Zhang¹, Hongbin Gao⁴, Xiangting Xu¹, Yi Han^2,3✉, Jianping Zhou¹, Wei Wang^1✉

1. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
2. Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, 9 Beiguan Street, Tongzhou District, Beijing 101149, China
3. Department of Surgical Laboratory, Beijing Tuberculosis and Thoracic Tumor Research Institute, 9 Beiguan Street, Tongzhou District, Beijing 101149, China
4. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
^* These authors contributed equally to this work.

✉ Corresponding author: Prof. Wei Wang, E-mail address: wangcpu209edu.cn; Prof. Yi Han, E-mail address: yhanbj2018com.

Abstract

Genetically engineered mesenchymal stem cells (MSCs), as non-viral gene delivery platforms, are rapidly evolving in tumor therapy due to their low immunogenicity and natural tumor-homing capacity.

Methods: In this paper, we selected reconstituted high-density lipoprotein (rHDL), a lipoprotein-bioinspired nanovector with specific binding ability to scavenger receptor B type I (SR-BI) expressed on MSCs, as a transfection agent to genetically modify MSCs. pDNA encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was used as a functional gene to be transfected into the nucleus of MSCs for TRAIL expression. Lauric acid-coupled polyethyleneimine (PEI-LA) as an amphiphilic cationic polymer was synthesized to electrostatically bind to pDNA, and then incorporated into rHDL to form rHDL/PEI-LA/pDNA nanoparticles.

Results: The nanoparticles exhibited homogenous particle size and excellent serum stability in vitro. Meanwhile, this SR-BI-targeted rHDL performed efficient intracellular gene delivery, specific lysosome-independent mechanism of cellular uptake and high transfection of pDNA towards MSCs. Moreover, high TRAIL expression in MSCs was detected after rHDL-mediated transfection. In vitro and in vivo results indicated that genetically engineered MSCs could accurately target to B16F10 cells, thereby producing significant apoptosis-inducing effect on aggressive melanoma.

Conclusion: TRAIL-expressing MSCs engineered by rHDL nanovector was an efficient and hypotoxic method for stem cells-based pulmonary melanoma metastasis-targeting therapy.

Keywords: Mesenchymal stem cells, reconstituted high-density lipoprotein, tumor-targeted therapy, tumor necrosis factor-related apoptosis-inducing ligand, pulmonary melanoma metastasis.

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