Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier

Abstract

Here, 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.

Iron and Copper Intracellular Chelation as an Anticancer Drug Strategy

“…al. reported the synthesis, characterization, and efficacy of Fe/Fe3O4-nanoparticles co-labeled with a tumor-homing and membrane-disrupting oligopeptide and the Fe chelator Dp44mT [ 181 ]. This Fe chelator and the peptide sequence PLFAERL (D[KLAKLAKKLAKLAK])CGKRK were conjugated to the surface of the nanoparticles using dopamine anchors [ 181 ].…”

“…reported the synthesis, characterization, and efficacy of Fe/Fe3O4-nanoparticles co-labeled with a tumor-homing and membrane-disrupting oligopeptide and the Fe chelator Dp44mT [ 181 ]. This Fe chelator and the peptide sequence PLFAERL (D[KLAKLAKKLAKLAK])CGKRK were conjugated to the surface of the nanoparticles using dopamine anchors [ 181 ]. The peptide sequence has two important parts, one responsible for tumor targeting and the other is responsible for the disruption of mitochondrial cell walls and triggering apoptosis [ 182 ].…”

“…The peptide sequence has two important parts, one responsible for tumor targeting and the other is responsible for the disruption of mitochondrial cell walls and triggering apoptosis [ 182 ]. In this study, the activity of the nanocarrier was tested on the highly metastatic 4T1 murine breast cancer cell line and was compared with a non-cancerous murine skin fibroblast cell line (MSFs) [ 181 ]. It was observed that at an optimal ratio of 1 to 3.2 of the peptide sequence and the Fe chelator, the IC 50 value was 2.2 times lower for the breast cancer cells than for the control cell line [ 181 ].…”

“…In this study, the activity of the nanocarrier was tested on the highly metastatic 4T1 murine breast cancer cell line and was compared with a non-cancerous murine skin fibroblast cell line (MSFs) [ 181 ]. It was observed that at an optimal ratio of 1 to 3.2 of the peptide sequence and the Fe chelator, the IC 50 value was 2.2 times lower for the breast cancer cells than for the control cell line [ 181 ]. These were encouraging results but further studies in different compositions of nano-carriers are necessary to achieve higher efficacies and better specificity.…”

Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia

“…Magnetic nanoparticles can be synthesized by using ionic and non-ionic techniques [43]. There are numerous methods known to synthesize magnetic nanoparticles, such as mechanical milling [44], co-precipitation [45], nanoreactor/microemulsion techniques [45,46], sonochemical processing [45,46], sol-gel methods [47], flow injection [43], electrochemical production [48], supercritical fluid techniques [49,50], thermal decomposition [13][14][15][16]22,[51][52][53][54][55], hydrothermal routes [45], microwave techniques [56], spray pyrolysis [45], laser pyrolysis [45], flame spray pyrolysis [45], gas phase synthesis [45], arc discharge [57], oxidation [58,59], and microbial methods etc. [43,45,60].…”