Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. free Dox (Fig. 8B). The results suggest that Apt-Dox tends to reduce the damage to MUC1-negative cells while retaining the efficacy of the doxorubicin against MUC1-positive cells. It should be noted that aptamer alone was nontoxic towards both cell lines, indicating that the aptamer itself was relatively safe to the cells and that the cytotoxicity was mainly caused by doxorubicin. Figure 8 Cell viability assays after the cells were treated with aptamer, free Dox, or Apt-Dox for 4 hours. Discussion The efficacy of chemotherapy is often limited by the adverse effects of cytotoxic agents that damage both cancer and normal cells. One strategy for reducing the adverse effects of chemotherapy is targeted drug delivery to cancer cells. MUC1 is considered a valuable target for ligand-guided anticancer chemotherapy due to its over-expression in most adenocarcinomas. Here in this study, using the SELEX technique and a peptide epitope of MUC1 as target, we developed a novel MUC1 aptamer (MA3) with a MA3 binding specificity for MUC1 still needs to be evaluated with extensive future animal studies. In this study, the uptake of doxorubicin by different cell lines was evaluated by confocal microscopy and flow cytometry. Free doxorubicin showed no preferential internalization in either MUC1-positive or MUC1-negative cells, presumably because the mechanism of uptake for free drug is similar for both cell lines (Fig. 7A and B). In contrast, Apt-Dox generated a doxorubicin fluorescence that was distinctively more potent in MUC1-positive cells as compared with that in MUC1-negative cells (Fig. 7C and D, 6E and F). This is a strong indication that Apt-Dox can discriminate efficiently between target and non-target cells. The mechanisms of uptake of free Dox and Apt-Dox by cells appear distinct. Unlike free Dox, which exclusively stained the nuclei (Fig. 7A), Apt-Dox generated both nuclear and cytosolic staining (Fig. 7C). While free doxorubicin could non-selectively enter cells via passive diffusion, the polar components of the DNA aptamer presumably would prevent the doxorubicin intercalated in Apt-Dox from freely defusing into the lipid cell membrane. It was possible that Apt-Dox entered MUC1-positive cells via receptor-mediated endocytosis [27], which occurred after Apt-Dox bound to the MUC1 structure buy 89-78-1 on A549 cell surface. Less entry of doxorubicin into HepG2 cells might come from lack of aptamer binding site on these MUC1-negative cells. As a result, a distinction in doxorubicin uptake between MUC1-positive and MUC1-negative cells was created. The cytotoxicity assay also supported the doxorubicin uptake data. For MUC1-positive cells, the cytotoxicity generated by Apt-Dox was similar to that generated by free doxorubicin; whereas for MUC1-negative cells, the cytotoxicity generated by Apt-Dox was reduced compared to that caused by free doxorubicin (Fig. 8, P<0.01). The data again suggested that the Apt-Dox could selectively deliver drug to buy 89-78-1 MUC1-positive cancer cells. This presumably would decrease the adverse effects of doxorubicin against normal tissues that are largely MUC1-negative. Many published studies on aptamer-guided targeted therapy employed nanoparticle (NP) as the carrier of anticancer agents [11], [28], [29]. However, it has also been reported that aptamer alone, without the carrier vehicle, could effectively deliver siRNA to tumor cells in vivo [30]. It would be interesting to know whether aptamer alone could also be employed WAF1 for delivery of cytotoxic drugs (such as doxorubicin) to tumor cells. To achieve this goal, the drug needs to be associated buy 89-78-1 with the aptamer, and the method for forming the aptamer-drug complex would probably influence the buy 89-78-1 therapeutic efficacy. It is possible that covalent conjugation of doxorubicin to the tumor-targeting ligand may decrease the drug efficacy, presumably buy 89-78-1 by altering the drug structure or by compromising the drug release from the targeting ligand [31]. Here in this study, the doxorubicin was not covalently conjugated to the aptamer, allowing the drug to be released more readily from the Apt-Dox complex. However, the in vivo stability of Apt-Dox complex is unknown at this stage, and extensive future research with in vivo animal studies is necessary to evaluate the stability of Apt-Dox in blood and tissues. In summary, a novel MUC1 aptamer MA3 is developed in this study. The Apt-Dox complex could selectively deliver the cytotoxic agent doxorubicin to MUC1-positive cells, while reducing the drug uptake by MUC1-negative cells. Since MUC1 is over-expressed in most adenocarcinomas, the aptamer may have potential utility as a guiding ligand for targeted chemotherapy against these malignancies. Nevertheless, extensive future research with animal models is still needed to evaluate the binding specificity of the aptamer. In addition, it is also necessary to explore.
Chemotherapy is a primary treatment for cancer, but its efficacy is
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a 67 kDa type I transmembrane glycoprotein present on myeloid progenitors
and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes
Apoptosis
bladder
brain
breast
cell cycle progression
cervix
CSP-B
Cyproterone acetate
EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck
EM9
endometrium
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F3
Goat polyclonal to IgG H+L)
Goat polyclonal to IgG H+L)Biotin)
GRK4
GSK1904529A
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Mapkap1
monocytes andgranulocytes. CD33 is absent on lymphocytes
Mouse monoclonal to CD33.CT65 reacts with CD33 andtigen
Palomid 529
platelets
PTK) or serine/threonine
Rabbit Polyclonal to ARNT.
Rabbit polyclonal to BMPR2
Rabbit Polyclonal to CCBP2.
Rabbit Polyclonal to EDG4
Rabbit polyclonal to EIF4E.
Rabbit polyclonal to IL11RA
Rabbit polyclonal to LRRIQ3
Rabbit Polyclonal to MCM3 phospho-Thr722)
Rabbit Polyclonal to RBM34
SB 216763
SKI-606
SNX-5422
STK) kinase catalytic domains. Epidermal Growth factor receptor
stomach
stomach and in squamous cell carcinoma.
TNFSF8
TSHR
VEGFA
vulva