چكيده به لاتين
Cancer is a significant fatal disease over the world. Within last decade, cancer therapy has been enhanced by using antibodies. For cancer therapy, cytotoxic drugs are used which have side effects on patients and destroy both health and unhealth cells. Combination of cytotoxisity of these drugs and high selectivity of antibodies can lead to efficient cancer therapy. Antibody can recognize antigenes of toumors' surface and delivers the cytotoxic drug to the target. The current approaches for cancer therapy are based on surgery, radiotherapy and chemotherapy, while the aforementioned strategy affects more efficiently. Using nanotechnology in the field of cancer therapy includes many scientific areas containing medicine, biology, engineer, chemistry and physics. Many materials in nanotechnology have been used for career diagnosis and therapy. For example, gold nanoparticles are used as carier for drug delivery in chemotherapy, treatment agent in photodynamics, gene, treatment of cancer of tissue and molecular imaging for diagnosis and prevention of cancer. Au nanoparticles exhibit unique structure, shape, size, being nontixicity and biocompatibility which result in efficient drug delivery and biomedical application. In general, using nanoparticles has been in the center of attraction due to easy entrance into the cells through endocytosis. In this regard, halloysite nanotubes have been used as the main framework of anticancer drug sandwiches. The space inside of these nanotubes provides drug loading oppurtunity, as well as silica lattice od outer surface of them can make covalent bonds with biological moieties. Note that all the parts individually demonstrated anticancer cheracteristics. ovarian tumor targeting by a modern biochemical medication is executed. preparation and characterization of a nanoscale suspension constructed of the natural halloysite nanotubes (with porous structure), gold nanoparticles (AuNPs in 10 nm diameter), docetaxel (as a cytotoxic anticancer agent), 3-chloropropyl trimethoxy silane (as a hydrophobic agent and linker for antibody attachment), and sortilin 2D8-E3 monoclonal antibody (a human IgG1 mAb), is well performed by various analytical methods. Application: anti-tumor activity of this novel designed smart high-tech conjugated medication is carefully studied on caov-4 (ATCC HTB76) cell line, which well expresses the sortilin 2D8-E3 mAb. The anti-cancer activity has been monitored via in vitro experiment. It has been revealed that effective drug delivery can be implemented through applying this novel nano-suspension (DTX@HNT/Au-SORT) with natural basis, and also an excellent controlled drug release is performed by the incorporated AuNPs into the pores of halloysite nanotubes (HNTs) and localized surface plasmon resonance (LSPR) activity. Moreover, great targeting has been obtained by the used sortilin 2D8-E3 mAb. To do a quantitative evaluation of cytotoxicity and cell killing potency (CKP), and selective function of DTX@HNT/Au-SORT nanoparticles, methyl tetrazolium (MTT) assay test was performed on two cell lines: caov-4 cancerous cells and 3T3 normal human cells. caov-4 cells were treated by three different concentrations of DTX@HNT/Au-SORT nano-suspension (10, 30, and 50 g/mL), in a totally 72-hours process. Besides, neat cultivated caov-4 ovarian cancerous cells, sole SORT mAb, the individual components including HNTs, DTX, and AuNPs, and binary therapeutic system DTX@HNT and DTX@HNT/Au were considered as the essential controls in a same concentration (50 g/mL). As observed in the figure, individual DTX shows similar CKP on both caov-4 and 3T3 cells, during a 72-h treatment. CKP values for the individual DTX are 62 ±2.8 % and 56 ±3.3 % on caov-4 and 3T3, respectively. Negative side effects resulting by administration of the sole DTX originate from this high CKP on the normal cells. In contrast, this is clearly observed that all three samples of DTX@HNT/Au-SORT nano-suspension have selectively affected on the caov-4 cells. only 10 ±3.7 % caov-4 cell viability is happened under treatment by DTX@HNT/Au-SORT (50 g/mL). As expected, this value was increased to 24 ±4.6 % and 39 ±2.2 % proportional to reducing the administrated dosage to 30 and 10 g/mL, respectively. Whereas, 84 ±1.3 % viability was observed by 3T3 cells under treatment by DTX@HNT/Au-SORT (50 g/mL), after passing the same time (72 h). From a comparison between therapeutic effect of DTX@HNT/Au and DTX@HNT/Au-SORT on caov-4 cell line, the significant role of SORT mAb is greatly highlighted. As can be seen, 48 ±3.9 % and 90 ±3.7 % CKP were observed by the same dosage of DTX@HNT/Au and DTX@HNT/Au-SORT, respectively, that the observed difference is attributed to SORT mAb. Generally, this is demonstrated by the charts that DTX is selectively delivered to caov-4 cancerous cells via this strategy and negligible influence on the normal human cells is observed. This partial influence likely coming from the leached DTX. Also, this is shown that the individual components like AuNPs solely influence on the cell viability. However, this selective delivery of DTX leads to low negative side effects resulting by DTX chemotherapy.
