文獻:線粒體、溶酶體和內(nèi)質(zhì)網(wǎng):哪個是光療的最佳靶點?
鏈接:https://www.sciencedirect.com/science/article/abs/pii/S0168365922006320
作者:李艷紅 ,賈浩然 ,王洪 銀,華先武 ,鮑彥文 ,吳福 根
節(jié)選:
為了實現(xiàn)上述目標,我們開發(fā)了一種基于含PS脂質(zhì)膠束的新型藥物遞送系統(tǒng)(方案1)。該膠束由PS共軛的1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-聚乙二醇(DSPE-PEG)分子(稱為DSPE-PEG-Ce6)自組裝而成,該分子由含羧基的二氫卟酚e6(Ce6)與含胺基的脂質(zhì)1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N- [氨基(聚乙二醇)-5000](銨鹽)(DSPE-PEG 5000 -NH 2)一步反應合成(原料DSPE-PEG 5000 -NH 2和產(chǎn)物DSPE-PEG-Ce6的分子結構見圖S1)。結果表明,制備的DSPE-PEG-Ce6能夠被癌細胞有效內(nèi)化并從線粒體遷移到溶酶體,最終到達內(nèi)質(zhì)網(wǎng)(ER)。此外,我們能夠通過調(diào)節(jié)DSPE-PEG-Ce6的細胞孵育濃度來精細地調(diào)節(jié)其細胞內(nèi)化量到相似的水平,并準確地比較其分別駐留在三種不同細胞器中的*效果。結果清楚地表明,與溶酶體和內(nèi)質(zhì)網(wǎng)靶向的光動力*相比,線粒體定位的光動力*取得了最*的*效果。總之,我們在此提供了一個理想的含PS膠束平臺,實現(xiàn)了DSPE-PEG-Ce6在細胞器間的動態(tài)跟蹤,并通過精確的時間和空間*增強了光動力*的療效,這可能代表了精準醫(yī)療的進步。
To achieve the above-mentioned goal, we developed a novel drug delivery system based on PS-containing lipid micelles (Scheme 1). The micelles were self-assembled by a PS-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG) molecule (termed DSPE-PEG-Ce6) synthesized by a one-step reaction between the carboxyl-containing chlorin e6 (Ce6) and the amine-containing lipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG5000-NH2) (the molecular structures of the raw material DSPE-PEG5000-NH2 and the product DSPE-PEG-Ce6 can be found in Fig. S1). The results showed that the as-prepared DSPE-PEG-Ce6 could be efficiently internalized by cancer cells and migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER). In addition, we were able to carefully tune the cellular internalization quantity of DSPE-PEG-Ce6 to a similar level by modulating its cell incubation concentration and accurately compare its therapeutic efficacy when it separately resided in the three different organelles. The results clearly showed that compared with the lysosome- and ER-targeted PDT, the mitochondrion-localized PDT achieved the most excellent therapeutic outcome. Taken together, we herein provided an ideal PS-containing micellar platform and realized the inter-organelle dynamic tracking of DSPE-PEG-Ce6 and enhanced PDT efficacy through precise temporal and spatial treatment, which may represent an advancement in precision medicine.
西安pg電子官方生物提供相關產(chǎn)品:
APRPG-PEG-DSPE
NGR-PEG-DSPE
NGR(c(GGCNGRC))-PEG-DSPE
RVG29-PEG-DSPE
THRPPMWSPVWP-PEG-DSPE
M2pep-PEG-DSPE
EB1-PEG-DSPE
CPP-PEG-DSPE
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