2025-02-13 作者：ZJ 来源：文献：cRGD target liposome delivery system promoted immunogenic cell death through enhanced anticancer potency of a thymidine conjugate under UVA activation as a cancer vaccine
文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1j7q0xp0qq4e0xq0by1w0m50qa543687&site=xueshu_se
作者：Rong Yang , Zhiwei Wang , Ying Yuan, Ting Qian, Qibing Zhou
相关产品：
DSPE-PEG (2000) 二硬脂酰磷脂酰胆碱-聚乙二醇2000
DSPE-PEG (2000)-mal 二硬脂酰磷脂酰胆碱-聚乙二醇2000-马来酰亚胺
原文摘要：Conventional chemotherapeutic and photodynamic therapy have recently been shown to also elicit immune response against cancer through the immunogenic cell death mechanism, which can be potentially translated into effective cancer vaccines. However, there are few studies on the potential of nanodelivery system to promote the immunogenic cell death as a cancer vaccine. We reported here that cRGD target liposome delivery system was capable to promote the immunogenic cell death through enhanced potency of a thymidine conjugate post UVA activation as a cancer vaccine. Liposomes and cRGD target liposomes were found to significantly increase the cellular accumulation of the thymidine conjugate and subsequently translated into enhanced cytotoxic potency after UVA activation. More importantly, cRGD target liposomes of the thymidine conjugate markedly promoted the early detection of immunogenic cell death markers including ATP, HMGB1 and calreticulin. Subsequent in vivo vaccination challenge study confirmed effective tumor growth inhibition by the cRGD liposomal thymidine conjugate and UVA treated cancer cells as the cancer vaccine. In addition, liposomes and cRGD
target liposomes alone did not shown any induction of the immunogenic cell death markers, revealing the adjuvant nature of the nanodelivery system.
DSPE-PEG-Mal是生物材料。DSPE部分具有亲脂性，它能使整个分子与脂质膜等生物膜结构产生亲和作用。中间的PEG（聚乙二醇）链段具有良好的水溶性和生物相容性，可增加材料在水性环境中的稳定性，减少与非特异性蛋白的相互作用。Mal（马来酰亚胺）基团是一种活性官能团。它能够与含有巯基的生物分子（如某些蛋白质、多肽等）在温和条件下发生特异性的化学反应，形成稳定的共价键。可用于制备靶向化合物递送系统，通过与具有巯基的靶向配体结合，实现化合物对特定细胞或组织的递送；也可用于对生物分子进行修饰，以改变其性质和功能。可用于制备cRGD靶脂质体当中，过程如下：
图：脂质体成分和2Cl化合物的化学结构
DSPE-PEG-cRGD的合成
DSPE-PEG-Mal，甲醇和水中加入cRGD在磷酸盐缓冲盐水中。所得到的混合物在室温下反应过夜，然后用甲醇淬灭。用制备的HPLC C18柱和三氟乙酸甲醇洗脱液分离理想产物。DSPE-PEG-cRGD作为一种脱色油收集，并通过1 H NMR和质谱分析进行确认。
脂质体的生成和2Cl化合物的装载
将DSPC、胆固醇和DSPE-PEG溶解在氯仿中。溶液被干燥成一层薄膜旋转蒸发，然后通过超声处理转化为水乳液。所需大小的脂质体挤微型挤出机。DSPC/DOPC或DOPC脂质体，1：1 DOPC/ DSPC或DOPC用于脂质体制备相同数量的胆固醇和DSPE-PEG。采用上述薄膜分散法，用DSPE-PEG/DSPE-PEG-cRGD和相同量的DSPC和胆固醇制备三种cRGD目标脂质体溶液。进行两种类型的2Cl化合物加载，每1 mL脂质体溶液加入0.5或0.17 mL 2Cl，然后在室温下进行涡旋和超声处理。
图：2cl负载脂质体和cRGD靶脂质体示意图
结论：cRGD靶脂质体传递系统能够通过增强UVA激活后的胸腺嘧啶偶联物来起作用。脂质体和cRGD靶脂质体可增加胸腺嘧啶偶联物的细胞积累，并在UVA激活后转化为增强的细胞有害性效力。更重要的是，cRGD靶向胸腺嘧啶结合物的脂质体促进了免疫原性细胞消除标志物的早期检测，包括ATP、HMGB1和钙网蛋白。
