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Dual secured nano-melittin for the safe and effective eradication of cancer cells.

ABSTRACT: The clinical application of natural and synthetic amphipathic peptides (e.g., melittin) for cancer therapy is hindered by their notorious side effect, lysing red blood cells. To safely deliver a therapeutic peptide to the tumor tissue and kill cancer cells, we developed an environment-sensitive peptide delivery system, dual secured nano-sting (DSNS), through the combination of a zwitterionic glycol chitosan and disulfide bonds. Melittin loaded DSNS could kill almost 100% of MCF-7, HCT-116, SKOV-3, and NCI/ADR-RES (multidrug resistant) cancer cells at the concentration of 5 ?M, while not showing any hemolytic effect.

SUBMITTER: Bei C

PROVIDER: S-EPMC4342614 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Dual secured nano-melittin for the safe and effective eradication of cancer cells.

Bei Cheng C Bindu Thapa T Remant K C KC Peisheng Xu X

Journal of materials chemistry. B 20141028 1

The clinical application of natural and synthetic amphipathic peptides (e.g., melittin) for cancer therapy is hindered by their notorious side effect, lysing red blood cells. To safely deliver a therapeutic peptide to the tumor tissue and kill cancer cells, we developed an environment-sensitive peptide delivery system, dual secured nano-sting (DSNS), through the combination of a zwitterionic glycol chitosan and disulfide bonds. Melittin loaded DSNS could kill almost 100% of MCF-7, HCT-116, SKOV- ...[more]

PMID: 25734006

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Project description:Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.Statement of significancePhotodynamic therapy (PDT) is increasingly used as a minimally invasive, controllable and effective therapeutic procedure for cancer treatment. However, complete eradication of tumor cells by PDT alone remains challenging. In this study, we investigate the potential of multilayer PDT in cancer treatment with high efficacy and low side effects. Through PDT targeting two cancer biomarkers located at distinct subcellular localizations, remarkable synergistic effects in cancer cell killing and tumor inhibition were observed in both in vitro and in vivo experiments. This strategy may be widely applied to treat various cancer types by using strategically designed PDT photosensitizers that target corresponding upregulated receptors at tactical subcellular localization.

Dataset Information

Dual secured nano-melittin for the safe and effective eradication of cancer cells.

Publications

Dual secured nano-melittin for the safe and effective eradication of cancer cells.

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