Theranostics 2019; 9(10):2984-2998. doi:10.7150/thno.31157
A TRAIL-Delivered Lipoprotein-Bioinspired Nanovector Engineering Stem Cell-Based Platform for Inhibition of Lung Metastasis of Melanoma
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.
Chen K, Cao X, Li M, Su Y, Li H, Xie M, Zhang Z, Gao H, Xu X, Han Y, Zhou J, Wang W. A TRAIL-Delivered Lipoprotein-Bioinspired Nanovector Engineering Stem Cell-Based Platform for Inhibition of Lung Metastasis of Melanoma. Theranostics 2019; 9(10):2984-2998. doi:10.7150/thno.31157. Available from http://www.thno.org/v09p2984.htm
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.