文獻(xiàn)：磷脂修飾的PEI基納米載體用于體內(nèi)siRNA*多藥耐藥*

鏈接：https://www.nature.com/articles/gt201497

作者：埃塞克斯郡南部G納瓦羅P·薩巴錢達(dá)尼，脈絡(luò)膜M Trivedi，S Movassaghian＆副總裁托爾奇林

節(jié)選：

實體瘤中P-糖蛋白過表達(dá)介導(dǎo)的多藥耐藥性(MDR)是多種化療失敗的主要因素。本研究評估了磷脂修飾的低分子量聚乙烯亞胺(DOPE-PEI)納米載體用于靜脈輸送*P-糖蛋白siRNA至*的效果，最終目標(biāo)是調(diào)控乳腺癌的MDR。首先，我們研究了DOPE-PEI納米載體的生物分布以及PEG涂層在皮下乳腺*模型中的作用。注射后四小時，PEG化載體通過增強(qiáng)的滲透性和滯留效應(yīng)，在實體瘤中積累了8%的注射劑量(ID)，由于PEG介導(dǎo)的循環(huán)時間延長，在血清中積累了22%的ID。其次，我們確定了DOPE-PEI/siRNA介導(dǎo)的P-gp下調(diào)聯(lián)合阿霉素(Dox)化療在MCF-7/MDR異種移植瘤中的療效和安全性。每周注射siRNA納米制劑和Dox，持續(xù)長達(dá)5周，使*對原本無效劑量的Dox產(chǎn)生敏感性，并使*體積與對照組相比縮小了三倍。這種對Dox療效的改善歸因于DOPE-PEI制劑介導(dǎo)的切除*中顯著的序列特異性P-gp下調(diào)。

Multidrug resistance (MDR) mediated by P-glycoprotein overexpression in solid tumors is a major factor in the failure of many forms of chemotherapy. Here we evaluated phospholipid-modified, low-molecular-weight polyethylenimine (DOPE-PEI) nanocarriers for intravenous delivery of anti-P-pg siRNA to tumors with the final goal of modulating MDR in breast cancer. First, we studied the biodistribution of DOPE-PEI nanocarriers and the effect of PEG coating in a subcutaneous breast tumor model. Four hours postinjection, PEGylated carriers showed an 8% injected dose (ID) accumulation in solid tumor via the enhanced permeability and retention effect and 22% ID in serum due to a prolonged, PEG-mediated circulation. Second, we established the therapeutic efficacy and safety of DOPE-PEI/siRNA-mediated P-gp downregulation in combination with doxorubicin (Dox) chemotherapy in MCF-7/MDR xenografts. Weekly injection of siRNA nanopreparations and Dox for up to 5 weeks sensitized the tumors to otherwise non-effective doses of Dox and decreased the tumor volume by threefold vs controls. This therapeutic improvement in response to Dox was attributed to the significant, sequence-specific P-gp downregulation in excised tumors mediated by the DOPE-PEI formulations.

西安齊岳生物提供相關(guān)產(chǎn)品：

DSPE-Pyrene

DSPE-Thiol

DSPE-PEG-GE11(二硬脂?；字Ｒ掖及?聚乙二醇-*細(xì)胞表皮生長因子EGFR靶向肽)

DSPE-PEG-His

DSPE-PEG-cRGD(二硬脂酰基磷脂酰乙醇胺-聚乙二醇-整合素靶向環(huán)肽)

ALC-0315

DOPE-PEG-Mal

DSPE-PEG-M2pep

DSPE-PEG-cisplatin

DSPE

GPC3靶向肽-PEG-DSPE

以上文章內(nèi)容來源各類期刊或文獻(xiàn)，如有侵權(quán)請聯(lián)系我們刪除！