一种新型人参皂苷Rk1修饰的卡巴他赛脂质体用于癌症靶向治疗

A novel cabazitaxel liposomes modified with ginsenoside Rk1 for cancer targeted therapy

黄丹丹 ¹唐忠捷 ¹蒲潇 ¹Wang Tianqi ²高飞燕 ¹李翀¹

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作者信息

1. 西南大学,重庆
2. 新加坡国立大学,新加坡
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摘要

[目的]制备一种人参皂苷Rk1修饰的卡巴他赛(CTX)脂质体(Rk1/CTX-Lip),以增强CTX的抗前列腺癌疗效,同时降低其治疗过程中的免疫抑制和全身毒性.[方法]采用薄膜水化法制备Rk1/CTX-Lip并考察其理化性质;分别在体外与体内评估Rk1/CTX-Lip的靶向性与长循环功能;构建小鼠皮下前列腺癌(RM-1)模型研究Rk1/CTX-Lip抗肿瘤效果;进一步通过肿瘤合并白色念珠菌感染模型肾脏真菌负荷、胸腺脾脏指数、脾脏免疫细胞占比、骨髓有核细胞计数等方法研究Rk1/CTX-Lip在肿瘤治疗过程中对机体免疫系统的调节功能;最后评估Rk1/CTX-Lip的生物相容性和体内安全性.[结果]我们成功制备了具有高CTX包封率(97.24±0.75％)和物理稳定性的Rk1/CTX-Lip.Rk1/CTX-Lip可以逃避巨噬细胞的吞噬,有效靶向肿瘤组织.与包载CTX的传统胆固醇脂质体(Chol/CTX-Lip)相比,尾静脉给药四次后Rk1/CTX-Lip平均肿瘤体积减少50％以上.此外,Rk1/CTX-Lip在抑制肿瘤生长的同时能够有效调节免疫器官和细胞,改善肿瘤治疗过程中的免疫抑制,减轻合并真菌感染的风险,同时具有优越的生物相容性与体内安全性.[结论]构建了一种人参皂苷Rk1修饰的卡巴他赛脂质体Rk1/CTX-Lip,该脂质体具有稳定性强、包封率高、安全性好等特点,体内外具有明显的肿瘤主动靶向和长循环功能,在提高卡巴他赛抗肿瘤药效的同时显著降低其毒副作用.该脂质体还能在肿瘤治疗过程中调节机体免疫系统,减轻合并真菌感染的风险,为免疫力低下的肿瘤患者抵抗合并真菌感染提供了新的思路,具有广泛的应用前景.

Abstract

Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTX-Lip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)％and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(＞50％)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.

关键词

人参皂苷Rk1/卡巴他赛/脂质体药物递送系统/前列腺癌/真菌感染

Key words

Cabazitaxel/Fungal infection/Ginsenoside Rk1/Liposome-drug delivery system/Prostate cancer

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基金项目

National Natural Science Foundation of China(82373808)

Chongqing Natural Science Foundation(cstc2021jcyjbshX0125)

Fundamental Research Funds for the Central Universities(SWURC2020001)

project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006)

出版年

2024

针灸和草药(英文)

天津中医药大学，中华中医药学会

针灸和草药(英文)

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参考文献量38

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