Because the induction of strong host antitumor responses plays a very important role in antitumor therapy, identifying effective approaches to elicit immunogenic cell death could have important implications. RIP3-dependent necroptotic cancer cells have been reported to release damage-associated molecular patterns and enhance antitumor immunity. In this study, hyaluronic acid-conjugated cationic liposomes (DOTAP/DOPE/PEG-DSPE/CHOL) (HA-P-LP) were prepared as a vector for mRIP3-pDNA overexpression in tumours. Compared with standard cationic liposomes, this vector markedly increased cellular gene internalisation in vitro, enhanced the tumour-targeting effect in vivo and exhibited a significant antitumor effect in combination with adjuvant chloroquine. Considering the dramatic increase in RIP3 under the pathological condition of pancreatitis and the correlation between pancreatitis and necroptosis, non-HA-conjugated liposomes with the same formulation loaded with shRNA mRIP3-pDNA effectively controlled the disease by decreasing the serum amylase concentration and inflammatory cell infiltration. The versatile cationic liposomes loaded with plasmids with opposing functions in this study provide a new concept and method for both tumour therapy and pancreatitis therapy.

由于诱导强烈的宿主抗肿瘤反应在抗肿瘤治疗中起着非常重要的作用，因此确定引发免疫原性细胞死亡的有效方法可能具有重要意义。据报道，依赖 RIP3 的坏死性癌细胞可以释放与损伤相关的分子模式并增强抗肿瘤免疫力。在本研究中，制备了透明质酸偶联的阳离子脂质体 (DOTAP/DOPE/PEG-DSPE/CHOL) (HA-P-LP) 作为在肿瘤中过表达 mRIP3-pDNA 的载体。与标准阳离子脂质体相比，该载体在体外显着增加了细胞基因内化，增强了体内肿瘤靶向作用。并与佐剂氯喹合用表现出显着的抗肿瘤作用。考虑到胰腺炎病理状态下 RIP3 的急剧增加以及胰腺炎与坏死性凋亡之间的相关性，负载 shRNA mRIP3-pDNA 的相同配方的非 HA 偶联脂质体通过降低血清淀粉酶浓度和炎症细胞浸润来有效控制疾病. 本研究中装载具有相反功能的质粒的多功能阳离子脂质体为肿瘤治疗和胰腺炎治疗提供了新的概念和方法。