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Sequential therapy for pancreatic cancer by losartan- and gemcitabine-loaded magnetic mesoporous spheres

机译：氯沙坦和吉西他滨负载磁性介孔球的胰腺癌顺序疗法

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摘要

Sequential therapy has attracted increasing attention for cancer treatment, in which multiple drugs can be used to enhance the therapeutic efficacy. In this work, sequential therapy is demonstrated using amino functionalized Fe3O4 embedded periodic mesoporous organosilica spheres (Fe3O4@PMO-NH2) and Fe3O4@PMO as drug carriers. Losartan can inhibit type I collagen and hyaluronic acid of the pancreatic cancer matrix, which is safe and inexpensive, and does not increase the risk of tumor metastasis. First, losartan is loaded in the Fe3O4@PMO-NH2 (Fe3O4@PMO-NH2-Los) to treat pancreatic cancer. Immunohistochemistry staining of tumor slices after treatment with Fe3O4@PMO-NH2-Los confirms that collagen and hyaluronan acid are significantly reduced. The major solid components in the extracellular matrix of the tumor are reduced, which facilitates the penetration of nanodrugs into the tumor site. Afterward, gemcitabine loaded Fe3O4@PMO (Fe3O4@PMO-Gem) is sequentially delivered to treat pancreatic cancer, which shows strong killing ability for the pancreatic cancer cells. Comparing with a saline group, the tumor volume treated with Fe3O4@PMO-NH2-Los, Fe3O4@PMO-Gem, and Fe3O4@PMO-NH2-Los + Fe3O4@PMO-Gem decreases to 92.6%, 60.7%, and 28.6%, respectively, suggesting that the sequential therapy significantly inhibits pancreatic tumor growth compared to the mono-therapy strategy. Taken together, this study provides a promising approach for nanomaterials-based sequential therapy for pancreatic cancer treatment.
机译：顺序治疗吸引了癌症治疗的越来越长，其中可以使用多种药物来增强治疗效果。在这项工作中，使用氨基官能化Fe3O4嵌入的周期性介孔有机血糖（Fe3O4 @ PMO-NH2）和Fe3O4作为药物载体的Fe3O4 @ PMO来证明顺序治疗。氯沙坦可以抑制胰腺癌基质的I型胶原蛋白和透明质酸，这是安全且廉价的，并且不会增加肿瘤转移的风险。首先，莱斯坦坦装载在Fe3O4 @ PMO-NH2（Fe3O4 @ PMO-NH2-LOS）中以治疗胰腺癌。用Fe3O4处理后肿瘤切片的免疫组织化学染色证实，胶原蛋白和透明质酸酸可显着降低。肿瘤细胞外基质中的主要固体组分减少，这有助于纳米粒子渗透到肿瘤部位。之后，吉西他滨装载Fe3O4 @ PMO（Fe3O4 @ PMO-Gem）被顺序地递送以治疗胰腺癌，这表现出胰腺癌细胞的强烈杀伤能力。与盐水组相比，用Fe3O4 @ PMO-NH2-LOS，Fe3O4 @ PMO-GEM和FE3O4 @ PMO-NH2-LOS + FE3O4 @ PMO-GEM的肿瘤体积与FE3O4-NH2-LOS，FE3O4-NH2-LOS + FE3O4降至92.6％，60.7％和28.6％分别表明，与单治疗策略相比，顺序治疗显着抑制胰腺肿瘤生长。在一起，本研究为胰腺癌治疗的纳米材料顺序治疗提供了有希望的纳米材料的顺序治疗方法。

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  • 来源
    《RSC Advances》 |2019年第34期|共9页
  • 作者

    Li Yanjun; Tang Yuxia; Chen Sui; Liu Ying; Wang Shouju; Tian Ying; Wang Chunyan; Teng Zhaogang; Lu Guangming;

  • 作者单位

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

    Nanjing Univ Sch Med Jinling Hosp Dept Med Imaging Nanjing 210002 Jiangsu Peoples R China;

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