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构建 ROS 响应性透明质酸修饰的紫杉醇和薯蓣皂苷元脂质体及协同增强抗卵巢癌作用的研究。

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

机构信息

Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People's Republic of China.

Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Jun 5;19:5193-5211. doi: 10.2147/IJN.S455942. eCollection 2024.

DOI:10.2147/IJN.S455942
PMID:38859958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11162966/
Abstract

PURPOSE

Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG-HA and DSPE-PEG-TK-PEG, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.

METHODS AND RESULTS

PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.

CONCLUSION

The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

摘要

目的

卵巢癌是一种致命的妇科恶性肿瘤，其腹部转移率很高。化疗对卵巢癌患者的临床预后仍然较差，细胞增殖和血管生成导致侵袭、迁移和复发。为了克服这些障碍，我们使用两种新型功能材料 DSPE-PEG-HA 和 DSPE-PEG-TK-PEG 构建了一种新型的 HA 修饰的紫杉醇和薯蓣皂苷元脂质体（PEG-TK-HA-PDLPs），将药物特异性递送至肿瘤部位，以减少 OC 细胞增殖和抗血管生成生成，从而抑制侵袭和迁移。

方法和结果

通过薄膜分散法制备了 PEG-TK-HA-PDLPs，具有理想的物理化学性质，并表现出主动靶向作用，增强了细胞摄取。使用在线 SynergyFinder 软件计算 PTX 和 Dios 的 ZIP 协同评分得 3.15，表明存在协同作用。体外结果表明，PEG-TK-HA-PDLPs 对 ID8 细胞具有高度细胞毒性，诱导 ID8 细胞凋亡，并抑制 ID8 细胞迁移和侵袭。体内研究表明，PEG-TK-HA-PDLPs 可以延长血液中的循环时间，在肿瘤部位显著积聚，并有效对抗血管生成，具有显著的抗肿瘤作用。

结论

PEG-TK-HA-PDLPs 的制备是治疗 OC 的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/00e87d93efb6/IJN-19-5193-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/1105aef09a5f/IJN-19-5193-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/1105aef09a5f/IJN-19-5193-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/b666d339f838/IJN-19-5193-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/bd20d6f81af2/IJN-19-5193-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/9ab36903b0d8/IJN-19-5193-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/6e6660797519/IJN-19-5193-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/967ce9c548f2/IJN-19-5193-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e37e/11162966/00e87d93efb6/IJN-19-5193-g0010.jpg

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