Department of Pharmaceutics and Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, PR China.
Department of Pharmacy, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
J Control Release. 2024 Sep;373:172-188. doi: 10.1016/j.jconrel.2024.07.009. Epub 2024 Jul 14.
Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.
卵巢癌是最致命的癌症之一,联合化疗和免疫疗法是对抗它的潜在策略。然而,联合疗法的抗癌疗效可能受到化疗和免疫疗法非选择性共递药的限制。在这里,使用 ID8 细胞膜(IM)和细菌外膜囊泡(OMV)分别设计了一种联合化疗和免疫疗法,以选择性地针对卵巢肿瘤(ID8)细胞和树突状细胞(DC)。多柔比星(DOX)和卵清蛋白(OVA)肽(OVA)分别被选为模型化疗和免疫治疗药物。选择了一种能够轻松加载 DOX 或 OVA 的 DNA 纳米立方作为载体。首先,使用 DNA 纳米立方来加载 DOX 或 OVA 以制备立方-DOX 或立方-OVA。然后,将纳米立方用 IM 包裹形成 IM@Cube-DOX,用 OMV 包裹形成 OMV@Cube-OVA。IM@Cube-DOX 可以被 ID8 细胞选择性摄取,导致有效的细胞杀伤,而 OMV@Cube-OVA 则在体外靶向并激活 DC2.4 细胞。在 C57BL/6 小鼠中,IM@Cube-DOX 和 OMV@Cube-OVA 均在 ID8 肿瘤处的积累增加。与非选择性递送方法(如 OMV@(Cube-DOX + Cube-OVA)或 IM@(Cube-DOX + Cube-OVA))相比,ID8-OVA 荷瘤小鼠的 IM@Cube-DOX + OMV@Cube-OVA 联合治疗表现出更好的抗肿瘤疗效。总之,这项研究展示了一种仿生递药策略,通过选择性递药策略,实现了肿瘤细胞和 DC 的选择性药物递药,从而增强了联合化疗和免疫疗法的抗肿瘤疗效。
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