载溶瘤呼肠孤病毒脂质体靶向治疗卵巢癌的实验研究

卵巢癌死亡率居妇科恶性肿瘤之首，亟待寻求新型高效的治疗策略以改善患者预后。溶瘤呼肠孤病毒(reovirus)为卵巢癌的治疗带来希望，但其疗效受限于中和抗体的作用。基于卵巢癌细胞高表达叶酸受体的特点，我们已成功制备了叶酸受体靶向脂质体包装reovirus的递送系统(F-PEG-LP-Reo)，证实PEG-LP-Reo可在卵巢癌腹水存在下仍对卵巢癌细胞发挥溶瘤作用，而不杀伤正常细胞。根据前期研究基础，我们推测F-PEG-LP-Reo可保护并靶向递送reovirus到肿瘤组织，促进凋亡、改善肿瘤免疫抑制微环境并逆转耐药,从而增强抗肿瘤效应。本项目以解决reovirus在临床应用中的关键技术障碍为目标，拟从分子、细胞及整体多个层面来评价F-PEG-LP-Reo在卵巢癌靶向治疗中的作用并探讨可能机制,有望为卵巢癌靶向治疗提供新策略。

The mortality rate of ovarian cancer ranks first among gynecological tumors, so it is urgent to find new and efficient strategies to improve survival rate. Reovirus brings hope for the treatment of ovarian cancer, but its efficacy is limited by neutralizing antibodies. Based on the characteristics of high expression of folate receptor on ovarian cancer cells, we have successfully made the folate receptor targeting liposome packaging reovirus (F-PEG-LP-Reo). It has been confirmed that PEG-LP-Reo can still play a tumor-lysing effect on ovarian cancer cells in the presence of ascites, but does not kill normal cells. Based on previous studies, we hypothesize that F-PEG-LP-Reo can protect and target delivery of reovirus to tumor tissue, promote apoptosis, improve tumor immunosuppressive microenvironment and reverse drug resistance, thus enhancing the anti-tumor effect. This project aims to solve the key technical obstacles of reovirus in clinical application, and intends to evaluate the role of F-PEG-LP-Reo in targeted therapy of ovarian cancer from the molecular, cellular and system levels and explore the possible mechanism, which is expected to provide a new strategy for ovarian cancer therapy.