Nasopharyngeal cancer-specific therapy based on fusion peptide-functionalized lipid nanoparticles.
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.
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, and ‡MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
Haiming
H
Luo
Lisen
L
Lu
Fei
F
Yang
Liang
L
Wang
Xiaoquan
X
Yang
Qingming
Q
Luo
Zhihong
Z
Zhang
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002277:Carcinoma; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D003287:Contrast Media; D004337:Drug Carriers; D008055:Lipids; D010455:Peptides; D011993:Recombinant Fusion Proteins