DSPE-PEG-cRGD 修飾策略在shRNA遞送脂質(zhì)體中的應(yīng)用

文獻(xiàn)：DSPE-PEG-cRGD修飾陽離子脂質(zhì)體的制備及其對(duì)乳腺癌的*腫瘤作用

鏈接：https://www.mdpi.com/1999-4923/14/10/2157

作者： 劉春燕，趙文麗，奧西德，張立剛，孫華敏，陳曦和鄧寧 

摘要：

陽離子脂質(zhì)體遞送干擾RNA（shRNA）在腫瘤*中發(fā)揮著重要作用。設(shè)計(jì)了環(huán)狀精氨酸-甘氨酸-天冬氨酸（cRGD）修飾的陽離子脂質(zhì)體（cRGD-CL），用于將ONECUT2（OC-2）shRNA（pshOC-2）靶向遞送至乳腺癌細(xì)胞。陽離子脂質(zhì)體的表征分析表明，制備的cRGD-CL/pshOC-2脂質(zhì)體復(fù)合物粒徑均一（150±1.02 nm），zeta電位適中（19.8±0.249 mV），包封率高達(dá)96%。流式細(xì)胞儀檢測(cè)結(jié)果表明，cRGD的引入可顯著促進(jìn)脂質(zhì)體靶向腫瘤細(xì)胞。在MCF-7細(xì)胞中，pshOC-2能夠下調(diào)OC-2的表達(dá)，導(dǎo)致細(xì)胞凋亡、細(xì)胞劃痕修復(fù)受阻、遷移和集落形成受阻，其中Bcl-xL和Bcl-2信號(hào)通路被抑制，Bax和Cleaved Caspase-3信號(hào)通路被上調(diào)。在MCF-7異種移植瘤小鼠中，靜脈注射cRGD-CL/pshOC-2脂質(zhì)體復(fù)合物可有效降低腫瘤組織中OC-2的表達(dá)，產(chǎn)生明顯的*腫瘤作用，提示該脂質(zhì)體復(fù)合物可能通過受體介導(dǎo)的胞吞轉(zhuǎn)運(yùn)作用深入腫瘤內(nèi)部。結(jié)果表明，陽離子脂質(zhì)體（cRGD-CL）是一種有效的OC-2 shRNA遞送系統(tǒng)，可能成為乳腺癌*的有效候選藥物。

Abstract

Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.

西安pg電子官方生物提供相關(guān)產(chǎn)品：

WYRGRL-PEG-DSPE

CTP-PEG-DSPE

CMP-PEG-DSPE

SHp-PEG-DSPE

CGKRK-PEG-DSPE

Xpeptide-PEG-DSPE

Asp6-PEG-DSPE

BR2-PEG-DSPE

CSTSMLKAC-PEG-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(qǐng)聯(lián)系我們刪除！