Nanoscale Melittin@Zeolitic Imidazolate Frameworks for Enhanced Anticancer Activity and Mechanism Analysis

The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate fra...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2018-07, Vol.10 (27), p.22974-22984
Main Authors: Li, Yawei, Xu, Na, Zhu, Wenhe, Wang, Lei, Liu, Bin, Zhang, Jianxu, Xie, Zhigang, Liu, Wensen
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Humans
Imidazoles - chemistry
Melitten - chemistry
Mice
Nanoparticles - chemistry
Signal Transduction - drug effects
Tumor Suppressor Protein p53 - metabolism
Zeolites - chemistry
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Summary:The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate framework-8 (MLT@ZIF-8) nanoparticles (NPs). The formed MLT@ZIF-8 NPs not only possess excellent stability but also efficiently inhibit the hemolysis bioactivity of MLT. Confocal scanning imaging and cytotoxicity experiments revealed that as-synthesized MLT@ZIF-8 NPs exhibit enhanced cellular uptake and cytotoxicity toward cancer cells compared to MLT. The mechanism is well investigated by a series of transcriptome analysis, which indicates that MLT@ZIF-8 NPs can regulate the expression of 3383 genes, and the PI3K/Akt-regulated p53 pathway is involved in MLT@ZIF-8 NPs induced A549 cells apoptosis. Finally, MLT@ZIF-8 NPs exhibit enhanced antitumor activity than free MLT in vivo, while no obvious systemic toxicity has been found. This work emphasizes the great potential of utilizing MOF as a simple and efficient nanoplatform for deliverying cytolytic peptides in cancer treatment, and also the investigation on the antitumor mechanism could provide theoretical support for clinical usage of MLT.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b06125