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Tumor Suppression In TNBC Via MiRNA Delivery By Targeted Cationic Liposome

Posted on:2018-02-19Degree:MasterType:Thesis
Country:ChinaCandidate:F XuFull Text:PDF
GTID:2494305966961739Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background: Breast Cancer(BC)is a kind of the most common invasive malignant tumor in female.Among the category of the whole kinds of BC,there is a special phenotype called Triple Negative Breast Cancer(TNBC),which was of deadly high invasiveness、clinical recurrence rate and distant metastasis rate,so as to a lack of effective treatment.Cationic liposome(CLPs)is a kind of common nano gene carrier systems,which has the potential to break the restriction of invalid drug targets through specific targeting modification and optimization of the physical and chemical properties and kinetic parameters.An ideal treatment effect could be hopefully get by a delivery of specific tumor suppressor genes targeted CLPs.Objective: For the sake of ideal TNBC treatment effect by specific tumor suppressor genes,a new kind of hyaluronic acid(HA)-targeted cationic liposome(HA-CLPs)was made and assessed of its targeting capacity、 biocompatibility and Biological effects.Methods: Film dispersion method was utilized and assessment of physicochemical property such as the representation of the size and zeta-potential was operated for the optimization.And then the HA targeting modification was made,with confocal and FCM(flow cytometry)used to assess its targeting capacity.Use Ed U cell proliferation test and cell wound scratch assay to assess biological effects.Assess the in-vivo treatment effects of mi RNA-loaded HA-CLPs by the modelling of tumor-burdened nude mice.Results and Conclusions: CLPs nano-particles were of good dispersibility and homogeneous form.Construction was hollow globe.The average size was(180.6±3.4)nm and the average zeta-potential was(43.4±2.8)mv.The average size of HA-targeted nano-particles and mi RNA-loaded HA-targeted nano-particles was(236.65±6.9)nm、(205.6±2.2)nm.The average zeta-potential of HAtargeted nano-particles and mi RNA-loaded HA-targeted nano-particles was(29.1±5.4)mv、(11.2±1.1)mv.Confocal and FCM methods verified the targeting capacity of HA-CLPs to transport mi R-205 around the MDA-MB-231 cell nucleus observably.Ed U cell proliferation test and cell wound scratch assay proved that mi R-205 and mi R-34 a sent into MDA-MB-231 cell had the ability to inhibit cell proliferation observably and at the same time,mi R-34 a had the ability to inhibit cell migration.The tumor-burdened nude mice which were dealt with mi RNA delivery had effective size reduction compared with blank control and NC,indicated that HACLPs gene delivery systems was of remarkable capacity in tumor inhibition in vivo.
Keywords/Search Tags:cationic liposome, HA(hyaluronic acid), TNBC(Triple Negative Breast Cancer), miRNA
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