Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier
AbstractHere, we report the synthesis, characterization, and efficacy study of Fe/Fe3O4-nanoparticles that were co-labeled with a tumor-homing and membrane-disrupting oligopeptide and the iron-chelator Dp44mT, which belongs to the group of the thiosemicarbazones. Dp44mT and the peptide sequence PLFAERL(D[KLAKLAKKLAKLAK])CGKRK were tethered to the surface of Fe/Fe3O4 core/shell nanoparticles by utilizing dopamine-anchors. The 26-mer contains two important sequences, which are the tumor targeting peptide CGKRK, and D[KLAKLAK]2, known to disrupt the mitochondrial cell walls and to initiate programmed cell death (apoptosis). It is noteworthy that Fe/Fe3O4 nanoparticles can also be used for MRI imaging purposes in live mammals. In a first step of this endeavor, the efficacy of this nanoplatform has been tested on the highly metastatic 4T1 breast cancer cell line. At the optimal ratio of PLFAERD[KLAKLAK]2CGKRK to Dp44mT of 1 to 3.2 at the surface of the dopamine-coated Fe/Fe3O4-nanocarrier, the IC50 value after 24 h of incubation was found to be 2.2 times lower for murine breast cancer cells (4T1) than for a murine fibroblast cell line used as control. Based on these encouraging results, the reported approach has the potential of leading to a new generation of nanoplatforms for cancer treatment with considerably enhanced selectivity towards tumor cells. View Full-Text
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Abayaweera, G.S.; Wang, H.; Shrestha, T.B.; Yu, J.; Angle, K.; Thapa, P.; Malalasekera, A.P.; Maurmann, L.; Troyer, D.L.; Bossmann, S.H. Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier. J. Funct. Biomater. 2017, 8, 23.
Abayaweera GS, Wang H, Shrestha TB, Yu J, Angle K, Thapa P, Malalasekera AP, Maurmann L, Troyer DL, Bossmann SH. Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier. Journal of Functional Biomaterials. 2017; 8(3):23.Chicago/Turabian Style
Abayaweera, Gayani S.; Wang, Hongwang; Shrestha, Tej B.; Yu, Jing; Angle, Kyle; Thapa, Prem; Malalasekera, Aruni P.; Maurmann, Leila; Troyer, Deryl L.; Bossmann, Stefan H. 2017. "Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier." J. Funct. Biomater. 8, no. 3: 23.
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