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Anti-CD20-liopsomes Encapsulated Vincristine In The Targeting Of Human Malignant Melanoma Stem Cell

Posted on:2015-12-18Degree:MasterType:Thesis
Country:ChinaCandidate:H SongFull Text:PDF
GTID:2284330422474893Subject:Cell biology
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The malignant melanoma is a kind of tumor cell, which majorly formed in theskin. It is a rare skin cancer, with higher degree of malignancy and high lethality inskin cancers. At present the only effective treatment is surgical removal of the tumorbefore it grows to1mm thickness. Tumor being treated at early stage can not recur in5years. So, the cure rate depends on early diagnosis and early treatment. Melanomahas poor prognosis, rate of patients with advanced five-year survival is only about10%. Therefore, tumor cell metastasis usually cause high rate of death.The precursor cells of malignant melanoma derive from mutant malignantmelanoma stem cells (MMSC). So removing melanoma stem cells firstly by drugstakes important role in curbing melanoma’s growth. Currently, insensitive treatmentof melanoma largely need drugs dose. Study found that MMSC secrete an antigenmaterial named CD20, which can be used perfect target of Nano-drugs; and liposomedrug delivery to target cells can reduce the drug dose and side effects.Liposome has been largely used in improving the traditional cancer treatments.The chemotherapy drugs based liposome as the carrier can reduce the side effects ofchemotherapy and effectively prevent the rapid degradation of the drug, which causedthe good performance of pharmacokinetics and achieve accumulation at the tumor site,with higher drug concentration. In the past20years, large chemotherapy drugs werepackaged in the carrier of Membrane phospholipids double molecule and these drugshave been utilized in the process of clinical development, or has been approved inclinical application. In the most forms of carriers approved in clinical, biodegradablepolymer nanoparticles and liposomes take up large parts. Liposomes, as a starNano-carriers formed of single or double phospholipid bilayer membranes, has beenwidely used for its excellent biocompatibility, good pharmacokinetic characteristics,and long time in vivo circulating. Recently, a number of liposome formulations have been approved for use in clinical practice, among which Doxil was the firstlipid-listed chemotherapy drugs approved in1995. However, liposomes cannotcontrol drug release. Liposomes may gather in vivo tumor but it is less targeting.Immunoliposome not only has targeting but also has efficiently drug delivery to thetumor site. Immunoliposome, as one of targeting preparation, has advantages of goodbiocompatibility, low toxicity, dose reduction, effectively avoiding drug resistance,long-acting, to protect the encapsulated drugs, to achieve precise targeting, effectivelycontrol drug release and improve patient medication compliance, etc.The melanoma cells in this subject has a high resistance to doxorubicin, so wechose to use sphingomyelin as the lipid liposomes timber, wrapped vincristine, andconnect the CD20antibody, to assemble to an immune which has good targeting,good biocompatibility and low dosage. The liposomes detected and produced by flowcytometer have targeted melanoma stem cells. Its size detected and produced byMalvern particle is even, in line with medication requirements. Spectrophotometerhelped us to measure liposome’s drug encapsulation efficiency and drug release.Liposome has been tested in vitro and in vivo for effectively killing melanoma stemand melanoma cells. This functional immune liposomes connecting active targetingCD20antibody show strong potential applications, which has a guiding significancefor clinical chemotherapy and nano anti-tumor carrier design.
Keywords/Search Tags:Anti-CD20antibody, Immunoliposome, Vincristine, Melanoma
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