Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment

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-methyla...

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Published in:Nano research 2022, Vol.15 (1), p.728-737
Main Authors: Huang, Shiqi, Deng, Lang, Zhang, Hanming, Wang, Luyao, Zhang, Yicong, Lin, Qing, Gong, Tao, Sun, Xun, Zhang, Zhirong, Zhang, Ling
Format: Article
Language:English
Subjects:
Anticancer properties
Apoptosis
Atomic/Molecular Structure and Spectra
Biomedicine
Biotechnology
Chemistry and Materials Science
Condensed Matter Physics
Fibronectin
Lungs
Materials Science
Melanoma
Metastases
Metastasis
Nanoparticles
Nanotechnology
Nutrition
Paclitaxel
Research Article
Survival
Toxicity
TRAIL protein
Tumor cells
Tumors
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Summary: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.
ISSN:1998-0124
1998-0000
DOI:10.1007/s12274-021-3553-2