Nasopharyngeal cancer-specific therapy based on fusion peptide-functionalized lipid nanoparticles.

Abstract

Current treatment of advanced-stage nasopharyngeal carcinoma (NPC) is not satisfactory. Targeted therapies offer hope for extending survival. Here, we developed simple, robust, and NPC-specific therapeutic lipid nanoparticles based on a fusion peptide, α-NTP, made up of an amphipathic α-helical peptide (α-peptide) linked to an NPC-specific therapeutic peptide (NTP). We found that α-NTP not only retained the sub-30 nm nanostructure-controlling ability of the α-peptide but also displayed the enhanced NPC-targeting ability of the NTP, in which the α-peptide accelerated the uptake of the NTP by NPC cells, with a 4.8-fold increase. Following uptake, α-NTP-based lipid nanoparticles (α-NTP-LNs) exerted coordinated cytotoxicity by inducing cell death via apoptosis and autophagy. In vivo and ex vivo optical imaging data showed that systemically administered α-NTP-LNs efficiently accumulated in the NPC xenograft tumor and displayed high contrast between tumor and normal tissues, which was further confirmed by flow cytometry that there had been a 13-fold uptake difference between tumor cells and hepatocytes. More importantly, the therapeutic efficacy of α-NTP-LNs was specific to NPC xenograft formed with 5-8F cells but not to fibrosarcoma xenograft formed with HT1080 cells in vivo. The growth of 5-8F tumors was significantly inhibited by α-NTP-LNs, with more than 85% inhibition relative to control groups (e.g., α-NTP and PBS treatment). In a lung metastasis model of NPC, survival was significantly improved by α-NTP-LN treatment. In a word, these excellent properties of α-NTP-LNs worked in sync and synergistically, maximizing the therapeutic efficacy of α-NTP-LNs against NPC and its metastasis.

• Authors: Haiming Luo, Lisen Lu, Fei Yang, Liang Wang, Xiaoquan Yang, Qingming Luo, Zhihong Zhang
• Journal: ACS nano (ACS Nano) Vol. 8 Issue 5 Pg. 4334-47 (May 27 2014) ISSN: 1936-086X [Electronic] United States
• PMID: 24766601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Drug Carriers
• Lipids
• Peptides
• Recombinant Fusion Proteins

Topics

• Animals
• Apoptosis
• Autophagy
• Carcinoma
• Cell Line, Tumor
• Circular Dichroism
• Contrast Media (chemistry)
• Drug Carriers
• Flow Cytometry
• Humans
• Lipids (chemistry)
• Mice
• Microscopy, Confocal
• Microscopy, Electron, Transmission
• Nanoparticles (chemistry)
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (drug therapy)
• Neoplasm Metastasis
• Neoplasm Transplantation
• Peptides (chemistry)
• Recombinant Fusion Proteins (chemistry)