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Amphiphilic irinotecan-melampomagnolide B conjugate nanoparticles for cancer chemotherapy

机译：两亲伊替替康 - Melampomagnolide B缀合物纳米粒子用于癌症化疗

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摘要

Melampomagnolide B (MMB) is a natural sesquiterpene lactone product structurally related to parthenolide (PTL). Although MMB has been widely used to treat various types of cancers, such as glioma, leukemia and colon cancer, the effective delivery of MMB to cancer cells remains a challenge. An amphiphilic drug-drug conjugate (ADDC) strategy has been proposed and developed as a promising drug self-delivery system for cancer therapy because of its simple preparation, carrier-free nature, and high therapeutic activity. Herein, we present a new ADDC, which is synthesized by linking the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug MMB through a carbonate bond. The obtained amphiphilic irinotecan-melampomagnolide B conjugate (Ir-C-MMB) can self-assemble in water into stable nanoparticles with an average diameter of around 122.1 nm. After cellular uptake, the carbonate bond between the hydrophilic drug and hydrophobic drug can be cleaved to release free Ir and MMB under acidic conditions, which exhibit a synergistic effect in tumor cells. MTT results reveal that the Ir-C-MMB nanoparticles can effectively inhibit proliferation of cancer cells. The apoptosis data indicate that the apoptosis rate of cells treated with Ir-C-MMB nanoparticles is about 50% within 24 h, which is much higher than that of free Ir or MMB. Our results suggest that this ADDC strategy could be used as a drug delivery platform for MMB and its derivatives, and that it offers effective synergistic therapeutic efficacy.
机译：Melampomagnolide B（MMB）是与阳离处（PTL）有关的天然索特萜烯内酯产物。虽然MMB已被广泛用于治疗各种类型的癌症，例如胶质瘤，白血病和结肠癌，但MMB对癌细胞的有效递送仍然是一个挑战。已经提出了两亲药物 - 药物缀合物（ADCC）策略，并作为癌症治疗的有希望的药物自我输送系统，因为其简单的制备，无载载体的性质和高治疗活性。在此，我们提出了一种新的ADCC，其通过将亲水抗癌药物伊替康（IR）和疏水抗癌药物MMB通过碳酸酯键将其与疏水性抗癌剂和疏水性抗癌药物MMB合成而合成。所得两亲氨基丙二烷 - Melampomagnolide B缀合物（IR-C-MMB）可以在水中自组装成稳定的纳米粒子，平均直径约为122.1nm。在细胞摄取后，可以在酸性条件下切割亲水药物和疏水药物之间的碳酸酯键，以在酸性条件下释放自由IR和MMB，这在肿瘤细胞中表现出协同作用。 MTT结果表明，IR-C-MMB纳米粒子可以有效抑制癌细胞的增殖。细胞凋亡数据表明，用IR-C-MMB纳米颗粒处理的细胞的凋亡率为24小时内的约50％，其远高于游离IR或MMB。我们的研究结果表明，该ADCC策略可用作MMB及其衍生物的药物递送平台，并提供有效的协同治疗效果。

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  • 来源
    《RSC Advances》 |2020年第15期|共9页
  • 作者

    Qu Wenhao; Yang Quanjun; Wang Guanchun; Wang Zhaohong; Huang Ping; Huang Wei; Zhang Rong; Yan Deyue;

  • 作者单位

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

    Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Pharm 600 Yishan Rd Shanghai 200233 Peoples R China;

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

    Southern Med Univ Fengxian Hosp Dept Obstet &

    Gynecol Shanghai 201499 Peoples R China;

    Shanghai Jiao Tong Univ State Key Lab Met Matrix Composites Sch Chem &

    Chem Engn 800 Dongchuan Rd Shanghai 200240 Peoples R China;

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