【摘要】：目的:本研究以經(jīng)檸檬酸改性的聚谷氨酸為載體,制備聚谷氨酸-順鉑復(fù)合物,接枝環(huán)RGD肽,以提高該復(fù)合物對(duì)腫瘤細(xì)胞的靶向性,同時(shí)對(duì)所得到的高分子-藥物復(fù)合物體外理化性質(zhì)和細(xì)胞毒作用、細(xì)胞攝取進(jìn)行評(píng)價(jià)。方法:以改性聚谷氨酸側(cè)鏈羧基與順鉑穩(wěn)定配位,再與RGD肽進(jìn)行化學(xué)偶聯(lián),得到修飾后的藥物復(fù)合物,對(duì)復(fù)合物的載藥量等性質(zhì)進(jìn)行了考察,同時(shí)采用人乳腺癌MDA-MB-231細(xì)胞和MCF-7細(xì)胞進(jìn)行了體外細(xì)胞生長抑制和細(xì)胞攝取行為的評(píng)價(jià)。結(jié)果:與未修飾的聚合物-藥物復(fù)合物(23.12%)比較,本研究所制備主動(dòng)靶向聚谷氨酸-順鉑復(fù)合物的載藥量略有下降(16.73%),體外釋放參數(shù)無顯著差異,表現(xiàn)出明顯的緩釋特征。體外細(xì)胞毒實(shí)驗(yàn)結(jié)果表明,兩類復(fù)合物保留了順鉑對(duì)腫瘤細(xì)胞的毒性,相比無RGD修飾的復(fù)合物,人乳腺癌MDA-MB-231和MCF-7細(xì)胞對(duì)RGD修飾的復(fù)合物攝取增強(qiáng)。結(jié)論:RGD修飾的順鉑-聚谷氨酸復(fù)合物成功制備,有利于提高針對(duì)體內(nèi)腫瘤的緩釋、靶向治療效果。
[Abstract]:Aim: to prepare polyglutamic acid-cisplatin complex with citric acid modified polyglutamic acid as carrier and graft cyclic RGD peptide to improve its targeting to tumor cells. At the same time, the physicochemical properties, cytotoxicity and cellular uptake of the polymer-drug complexes in vitro were evaluated. Methods: the modified poly (glutamic acid) side chain carboxyl group was stably coordinated with cisplatin, then chemically coupled with RGD peptide to obtain the modified drug complex. Human breast cancer MDA-MB-231 cells and MCF-7 cells were used to evaluate cell growth inhibition and cell uptake in vitro. Results: compared with unmodified polymer-drug complexes (23.12%), the amount of active target polyglutamic acid-cisplatin complexes was slightly decreased (16.73%), and there was no significant difference in vitro release parameters. It shows obvious slow release characteristics. The results of cytotoxicity test in vitro showed that the two kinds of complexes retained the toxicity of cisplatin to tumor cells. Compared with the complexes without RGD modification, the uptake of RGD modified complexes by MDA-MB-231 and MCF-7 cells of human breast cancer increased. Conclusion: the successful preparation of RGD modified cisplatin-polyglutamic acid complex is beneficial to improve the sustained release and target therapeutic effect of tumor in vivo.
【作者單位】： 中國藥科大學(xué)藥學(xué)院;
【基金】：中央高校基本科研業(yè)務(wù)費(fèi)科研專項(xiàng)基金(ZJ14141)
【分類號(hào)】：R943;R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 胡秀麗;謝志剛;黃宇彬;景遐斌;;高分子藥物學(xué)的研究進(jìn)展與期盼[J];高分子學(xué)報(bào);2013年06期

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李貴平;張輝;池曉華;黃凱;;多肽受體介導(dǎo)的放射性核素靶向治療的研究進(jìn)展(文獻(xiàn)綜述)[J];放射免疫學(xué)雜志;2010年03期

2 閆強(qiáng);趙越;;二氧化碳響應(yīng)性聚合物及其應(yīng)用進(jìn)展[J];高分子材料科學(xué)與工程;2014年02期

3 孫博薇;王偉;曹延武;劉瑞紅;趙燕軍;王征;;熱響應(yīng)納米金球作為非共價(jià)藥物載體合成及性質(zhì)研究[J];高分子學(xué)報(bào);2014年05期

4 劉東紅;丁建勛;許維國;宋曉峰;莊秀麗;陳學(xué)思;;四臂聚乙二醇-聚丙交酯立體復(fù)合膠束及其藥物傳輸性能[J];高分子學(xué)報(bào);2014年09期

5 Yan Zhang;Xiao-ju Wang;Miao Guo;閻虎生;Chen-hong Wang;劉克良;;Cisplatin-loaded Polymer/Magnetite Composite Nanoparticles as Multifunctional Therapeutic Nanomedicine[J];Chinese Journal of Polymer Science;2014年10期

6 Yi-fei Li;Hai-yang Yu;Hai Sun;劉建國;湯朝暉;Dan Wang;Lian-you Yu;Xue-si Chen;;Cisplatin-loaded Poly(L-glutamic acid)-g-Methoxy Poly(ethylene glycol) Nanoparticles as a Potential Chemotherapeutic Agent against Osteosarcoma[J];Chinese Journal of Polymer Science;2015年05期

7 閆丹;郭慧琛;馮霞;靳野;魏衍全;孫世琪;;口蹄疫病毒樣顆粒作為抗癌藥物載體的條件探索[J];安徽農(nóng)業(yè)科學(xué);2015年13期

8 ;Radiolabeling and evaluation of ~(188)Re-RGD as an agent for α_vβ_3 receptor expression[J];Nuclear Science and Techniques;2012年01期

9 馬玉飛;于俊峰;周偉;沈華;胡偉青;尹端l，

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