本文選題：卵巢癌 + 中空介孔二氧化硅納米��； 參考：《南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版)》2017年09期

【摘要】：目的:構(gòu)建中空介孔二氧化硅納米(hollow mesoporous silica nanoparticles,HMSN)復(fù)合載藥系統(tǒng)靶向作用于卵巢癌細(xì)胞,評(píng)估此復(fù)合藥物運(yùn)載系統(tǒng)的作用,探究胰島素樣生長(zhǎng)因子1受體(insulin-like growth factor receptor,IGF-1R)特異性抑制劑NVP通過(guò)HMSN運(yùn)載系統(tǒng)聯(lián)合阿霉素(doxorubicin,DOX)對(duì)卵巢癌的治療效果。方法:在HMSN表面修飾羧基,通過(guò)機(jī)械攪拌和靜電吸引作用包載DOX和熒光NVP構(gòu)建HMSN復(fù)合載藥系統(tǒng);采用透射電鏡、紅外光譜儀、Zeta電位等方法表征此載藥系統(tǒng);檢測(cè)HMSN載藥系統(tǒng)中DOX和熒光NVP在不同pH值環(huán)境中的釋放率;通過(guò)熒光共聚焦顯微鏡觀察藥物運(yùn)載系統(tǒng)不同時(shí)間點(diǎn)在細(xì)胞中的聚集情況;將實(shí)驗(yàn)分為HMSN-DOX-NVP組、HMSN-DOX組和游離對(duì)照組,分別作用于卵巢癌SKOV-3細(xì)胞株,MTT法檢測(cè)3組細(xì)胞的抑制率,并通過(guò)流式細(xì)胞儀檢測(cè)3組細(xì)胞的凋亡率。結(jié)果:HMSN在修飾羧基之前所帶電荷為-22.3 mV,在其表面修飾羧基后,HMSN所帶負(fù)電荷增多至-44.9 mV;HMSN負(fù)載藥物后,其形態(tài)和粒徑均未發(fā)生改變;HMSN復(fù)合載藥系統(tǒng)所處環(huán)境的p H值逐漸降低時(shí),DOX和熒光NVP的釋放率逐漸升高;HMSN-DOX-NVP及HMSN-DOX可在細(xì)胞中聚集,并可隨著作用時(shí)間的延長(zhǎng)逐漸滲透進(jìn)入胞核釋放藥物。HMSN-DOX-NVP組的細(xì)胞凋亡率和抑制率均高于HMSN-DOX組和游離對(duì)照組(P0.05)。結(jié)論:HMSN復(fù)合載藥系統(tǒng)通過(guò)非特異性的內(nèi)吞途徑可以良好聚集在胞中釋放藥物并可保證藥物活性,NVP聯(lián)合DOX可提高DOX對(duì)卵巢癌細(xì)胞的殺傷率并實(shí)現(xiàn)針對(duì)IGF-1R的靶向抑制。
[Abstract]:Objective: to construct a hollow mesoporous silica nano (hollow mesoporous silica nanoparticles, HMSN) compound drug delivery system to target ovarian cancer cells, evaluate the role of the compound drug delivery system and explore the specific inhibitor of the insulin like growth factor 1 receptor (insulin-like growth factor receptor, IGF-1R) NVP through HMSN The therapeutic effect of system combined with doxorubicin (DOX) on ovarian cancer. Methods: modify the carboxyl group on the surface of HMSN, construct HMSN compound drug loading system by mechanical agitation and electrostatic attraction, encapsulate DOX and fluorescent NVP, and use transmission electron microscope, infrared spectrometer, Zeta potential and other methods to characterize the drug carrying system, and detect DOX and fluorescein in HMSN carrier system. The release rate of light NVP in different pH environment; the aggregation of the drug delivery system at different time points was observed by fluorescence confocal microscope; the experiment was divided into HMSN-DOX-NVP group, HMSN-DOX group and free control group, which acted on the SKOV-3 cell line of ovarian cancer, and the inhibition rate of 3 groups of cells was detected by MTT method, and the flow cytometry was used. The apoptosis rate of 3 groups of cells was detected. Results: the charge of HMSN before the modified carboxyl group was -22.3 mV, and the negative charge of HMSN increased to -44.9 mV after the surface modification of the carboxyl group. The morphology and particle size of the HMSN loaded drugs were not changed; when the P H value of the HMSN compound carrier system was gradually reduced, the release rate of DOX and fluorescent NVP was gradual. HMSN-DOX-NVP and HMSN-DOX could accumulate in the cells, and the apoptosis rate and inhibition rate of.HMSN-DOX-NVP group were higher than that of group HMSN-DOX and free control group (P0.05). Conclusion: the HMSN compound drug carrying system can gather in the cell well through the non specific endocytic pathway. Drug release and drug activity can be ensured. NVP combined with DOX can increase the killing rate of DOX to ovarian cancer cells and achieve targeted inhibition of IGF-1R.
【作者單位】： 東南大學(xué)醫(yī)學(xué)院臨床醫(yī)學(xué)系;東南大學(xué)附屬中大醫(yī)院婦產(chǎn)科;
【基金】：江蘇省婦幼保健科研項(xiàng)目(F201351)
【分類號(hào)】：R737.31
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本文編號(hào)：2074671