文献:
Theranostic liposomes containing conjugated polymer dots and doxorubicin for bio-imaging and targeting therapeutic delivery
文献链接:
https://pubs.rsc.org/en/content/articlelanding/2016/ra/c5ra24485d作者:
Man Ma, Mingzhu Lei, Xiaoxiao Tan, Fengping Tan, Nan Li
相关产品:
1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)(二棕榈酰磷脂酰胆碱)
DSPE-PEG2000-FA(二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000-叶酸)
原文摘要:
This work was devoted to the development of a lipid-based theranostic nanoparticle able to simultaneously host conjugated polymer dots, doxorubicin (Dox) and folate acid (FA). Poly(9,9-dioctylfluorene-2,7-diyl-co-benzothiadiazole) (PFBT) was chosen as the fluorescent probe because of its high brightness in vitro cellular uptake study and good biocompatibility in vitro/in vivo toxicity experiment. The theranostic liposomes (PFBT-Dox-Lip-FA) exhibited a hydrodynamic size of 127.30 ± 3.20 (nm) with a zeta potential of −25.00 ± 2.00 (mV). Mostly importantly, the extent of Dox release at 24 h from PFBT-Dox-Lip-FA showed a satisfied result at the condition of mild hyperthermia compared with Dox-Lip-FA. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in MCF-7 cells at 16.8 ± 4.5 (µg/mL), whereas the IC50 of Dox-Lip-FA (37 °C) was 28.3 ± 3.7 (µg/mL). The cellular uptake study also revealed higher drug accumulation in tumor cells for theranostic liposomes. In vivo studies of PFBT-Dox-Lip-FA on tumor-bearing mouse models revealed that the distribution of liposomes in tumor could be indicated accurately by PFBT. Besides, tumor-bearing mice could be significantly inhibited by PFBT-Dox-Lip-FA. Together with the negligible in vivo toxicity, PFBT-Dox-Lip-FA, was a useful system for simultaneous cancer diagnosis and targeting drug delivery.
DSPE - PEG2000 - FA 是一种具有多种功能的生物活性分子。它主要由三部分组成:DSPE(1,2 -二硬脂酰- sn -甘油- 3 -磷酸乙醇胺)、PEG2000(聚乙二醇,分子量约为 2000)和 FA(叶酸,folic acid)。DSPE 部分是磷脂,含有亲水性的磷酸乙醇胺头部和两条疏水性的脂肪酸链,这使得分子具有一定的亲脂性。PEG2000 是亲水性的聚合物链,能增加分子在水中的溶解度、改善生物相容性和延长循环时间。FA 是一种维生素,在这个分子中作为靶向基团,能够特异性地与叶酸受体结合。该文献基于DSPE - PEG2000 - FA 制备了脂质纳米颗粒,过程如下:
图:作用机制图
DSPE - PEG2000 - FA在阿霉素包裹脂质体的制备:
采用硫酸铵梯度法将阿霉素包裹成脂质体。将DPPC、DSPE-PEG2000-FA和氯仿中的胆固醇以DPPC、胆固醇、 DSPE-PEG2000-FA 按一定的比例混合在一个圆底烧瓶中。然后蒸发混合物,去除溶剂,制作出一层薄膜。得到的薄膜分散在硫酸铵中,用温和的涡流水化。悬浮液分别用不同的孔径膜进行挤压。在室温下透析,去除游离的硫酸铵。然后将阿霉素以一定比例的化合物-血脂摩尔比溶解在溶液中孵育。负载dox的脂质体存储在适合温度下,以供以后使用。用氯化钠进行透析,去除未捕获的化合物。分离后,用荧光光谱仪测定脂质体内的阿霉素捕获量。
氟探针的脂质体的制备:
实验重复进行几次,数据以平均± SD表示。为了制备载有氟探针的脂质体,将上述脂质和荧光探针(PFBT或Dio)溶解在氯仿中,减压蒸发。所得到的薄膜用与上述方法相同的方法进行水合。载氟探针的脂质体保存在适宜温度以供以后使用。
图:表征图像
结论:
该文献利用DSPE - PEG2000 - FA成功制备阿霉素包裹脂质体,然后又在配方中引用PFBT,使其双分子层结构紧凑,最终得到PFBT嵌入式和dox负载脂质体的平台,具有靶向性用于裸鼠的cancer成像。