1. Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment
- Author
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Luyao Wang, Lang Deng, Xun Sun, Hanming Zhang, Ling Zhang, Yicong Zhang, Tao Gong, Zhirong Zhang, Shiqi Huang, and Qing Lin
- Subjects
02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Metastasis ,chemistry.chemical_compound ,medicine ,General Materials Science ,Lung Melanoma ,Electrical and Electronic Engineering ,Survival rate ,Lung ,biology ,Chemistry ,Melanoma ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Fibronectin ,medicine.anatomical_structure ,Paclitaxel ,Cancer research ,biology.protein ,Tumor necrosis factor alpha ,0210 nano-technology - Abstract
Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung, leading to sharply reduced patients’ survival rate. Effectively treating these tumors thus could improve late stage melanoma with lung metastasis. In this study, we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu (CR(NMe)EKA) decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PTX) to lung melanoma tumor sites (TRAIL-[ND-PTX]CR(NMe)EKA). These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles, while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs. The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply, leading to stronger overall anti-tumor effect. This TRAIL-[ND-PTX]CR(NMe)EKA system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice, without displaying significant toxicity. Hence, this designing strategy and the fabricated nanoplatform possess potential for further development.
- Published
- 2021