A new hexapeptide from the leader peptide of rMnSOD enters cells through the oestrogen receptor to deliver therapeutic molecules

被引:10
作者
Borrelli, Antonella [1 ]
Schiattarella, Antonietta [9 ]
Mancini, Roberto [6 ]
Pica, Alessandra [2 ]
Pollio, Maria Laura [2 ]
Ruggiero, Maria Grazia [2 ]
Bonelli, Patrizia [1 ]
De Luca, Viviana [3 ]
Tuccillo, Franca Maria [1 ]
Capasso, Clemente [3 ]
Gori, Enrico [4 ]
Sanseverino, Marina [5 ]
Carpentieri, Andrea [7 ]
Birolo, Leila [7 ]
Pucci, Piero [7 ]
Rommelaere, Jean [8 ]
Mancini, Aldo [9 ]
机构
[1] Fdn Pascale, Natl Canc Inst, Mol Biol & Viral Oncol, Naples, Italy
[2] Univ Naples Federico II, Federico 2, Dept Biol, I-80138 Naples, Italy
[3] CNR, Inst Prot Biochem, Naples, Italy
[4] Univ Udine, Dept Stat, Udine, Italy
[5] CNR, INBIOS Inst Genet & Biophys, Naples, Italy
[6] Friedrich Loeffler Inst, Dept Biotechnol, Neustadt, Germany
[7] Univ Naples Federico II, Federico 2, Dept Chem Sci, I-80138 Naples, Italy
[8] Deutsch Krebsforschungszentrum, Infect & Canc Program, Abt F010, Heidelberg, Germany
[9] Laedhexa Biotechnol Inc, QB3 953, San Francisco, CA 94107 USA
关键词
MANGANESE SUPEROXIDE-DISMUTASE; BREAST-CANCER CELLS; RECOMBINANT MNSOD; GENE-EXPRESSION; CISPLATIN; TUMOR; APOPTOSIS; GROWTH; SENSITIVITY; OVEREXPRESSION;
D O I
10.1038/srep18691
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER+ cells for diagnostic purposes and clinical or immune therapy.
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页数:13
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