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葉酸修飾的載藥相變納米粒靶向治療裸鼠移植瘤的研究

發(fā)布時(shí)間:2018-03-27 18:43

  本文選題:靶向 切入點(diǎn):載藥 出處:《中國(guó)超聲醫(yī)學(xué)雜志》2017年10期


【摘要】:目的研究葉酸受體靶向的、載紫杉醇(PTX)的相變納米粒造影劑(FR-PTX-PNPCA)對(duì)裸鼠卵巢癌移植瘤的治療作用。方法選取載卵巢癌移植瘤的裸鼠60只,隨機(jī)等分為6組,每隔3d分別通過(guò)尾靜脈注射藥物200μl,記錄腫瘤生長(zhǎng)情況。A組為注射生理鹽水+超聲,即注射生理鹽水后用治療超聲輻照;B組為單純FR-PTX-PNPCA;C組為FR-PTX-PNPCA+超聲,即注射FR-PTX-PNPCA后用超聲輻照;D組為非靶向的載藥相變納米粒PTX-PNPCA+超聲;E組為靶向載藥的非相變納米粒FR-PTX-NPCA+超聲;F組為Taxol組。于第二次給藥后2h每組處死5只裸鼠,取內(nèi)臟及腫瘤組織勻漿觀察PTX在體內(nèi)的分布情況。2周后處死剩余裸鼠,測(cè)量腫瘤大小,并將腫瘤切片作免疫組化,觀察治療效果。結(jié)果各組中肝臟和脾臟的PTX濃度最高,C組腫瘤內(nèi)的PTX濃度在各組中最高;治療后A、B、D、E組和F組腫瘤大小無(wú)明顯差異,C組腫瘤較以上各組明顯較小,并且C組內(nèi)的腫瘤細(xì)胞增值率和凋亡率與以上各組也有顯著差異。結(jié)論研究表明,經(jīng)靜脈注射FR-PTX-PNPCA能靶向釋放藥物,治療裸鼠移植瘤,其機(jī)制可能與FR-PTX-PNPCA能靶向腫瘤細(xì)胞,并在超聲作用下與相變釋放藥物有關(guān),具體機(jī)制有待進(jìn)一步研究。
[Abstract]:Objective to study the therapeutic effect of folate receptor-targeted, paclitaxel-loaded phase change nanoparticles (PNPCA-FR-PTX-PNPCA) on transplanted ovarian cancer in nude mice. Methods 60 nude mice carrying ovarian cancer were randomly divided into 6 groups. Every 3 days, 200 渭 l of the drug was injected through the tail vein. The growth of tumor was recorded. Group A was injected with normal saline ultrasound, and group B was irradiated by therapeutic ultrasound after injection of normal saline. Group B was treated with FR-PTX-PNPCAA C and group C was treated with FR-PTX-PNPCA ultrasound. After injection of FR-PTX-PNPCA, five nude mice were killed in each group 2 h after injection of FR-PTX-PNPCA. Group D was irradiated by ultrasound with phase change nanoparticle PTX-PNPCA as non-target carrier, group E as target drug carrying drug, group F with non-phase change nanoparticles FR-PTX-NPCA ultrasound and group F as Taxol group. 2 hours after the second administration of the drug, 5 nude mice were killed in each group, and 5 nude mice were killed in each group 2 hours after the second administration of the drug. The visceral organs and tumor homogenate were taken to observe the distribution of PTX in vivo. 2 weeks later, the remaining nude mice were killed, the tumor size was measured, and the tumor sections were stained with immunohistochemistry. Results the PTX concentration of liver and spleen in group C was the highest in each group, and the tumor size of group C was significantly smaller than that of group C after treatment, and there was no significant difference in tumor size between group E and group F after treatment. The proliferation rate and apoptosis rate of tumor cells in group C were also significantly different from those in the above groups. Conclusion the results show that intravenous injection of FR-PTX-PNPCA can target the release of drugs and treat xenograft tumors in nude mice, and its mechanism may be similar to that of FR-PTX-PNPCA targeting tumor cells. The mechanism of phase-change release drug is to be further studied.
【作者單位】: 重慶醫(yī)科大學(xué)附屬成都第二臨床學(xué)院成都市第三人民醫(yī)院;
【基金】:國(guó)家自然基金青年基金項(xiàng)目(No.81401433)
【分類號(hào)】:R445.1;R737.31

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