Zhang Qixiong, Zhang Fuzhong, Li Shanshan, Liu Renfeng, Jin Taotao, Dou Yin, Zhou Zhenhua, Zhang Jianxiang
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
Department of Pharmaceutical Engineering, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Theranostics. 2019 May 31;9(13):3732-3753. doi: 10.7150/thno.34377. eCollection 2019.
Colitis-associated colon cancer (CAC) is a widely recognized cancer, while treatment with the existing chemotherapeutic drugs affords limited clinical benefits. Herein we proposed a site-specific, combination nanotherapy strategy for targeted treatment of CAC by the oral route. : A reactive oxygen species (ROS)-responsive and hydrogen peroxide-eliminating material OCD was synthesized, which was further produced into a functional nanoparticle (OCD NP). The antioxidative stress and anti-inflammatory effects of OCD NP were examined by and experiments. By packaging an anticancer drug camptothecin-11 (CPT-11) into OCD NP, a ROS-responsive nanotherapy CPT-11/OCD NP was obtained, and its antitumor activity was evaluated by both and studies. Preliminary safety studies were also performed for CPT-11/OCD NP in mice. : OCD NP significantly attenuated oxidative stress and inhibited inflammatory response in different cells and mice with induced colitis. CPT-11/OCD NP could selectively release drug molecules under intestinal pH conditions and at high levels of ROS. In C26 murine colon carcinoma cells, this nanotherapy showed significantly higher antitumor activity compared to free CPT-11 and a non-responsive CPT-11 nanotherapy. Correspondingly, oral delivery of CPT-11/OCD NP notably inhibited tumorigenesis and tumor growth in mice with induced CAC. By combination therapy with the nanovehicle OCD NP in the inflammatory phase, more desirable therapeutic effects were achieved. Furthermore, CPT-11/OCD NP displayed excellent safety profile for oral administration at a dose that is 87.3-fold higher than that employed in therapeutic studies. : Anticancer nanotherapies derived from intrinsic anti-inflammatory nanocarriers are promising for targeted combination treatment of inflammation-associated tumors by simultaneously shaping pro-inflammatory microenvironment toward a relatively normal niche sensitive to chemotherapy.
结肠炎相关结肠癌（CAC）是一种广为人知的癌症，而现有化疗药物的治疗所带来的临床益处有限。在此，我们提出了一种通过口服途径靶向治疗CAC的位点特异性联合纳米治疗策略。：合成了一种活性氧（ROS）响应性且能消除过氧化氢的材料OCD，并将其进一步制成功能性纳米颗粒（OCD NP）。通过[具体实验1]和[具体实验2]实验研究了OCD NP的抗氧化应激和抗炎作用。通过将抗癌药物喜树碱-11（CPT-11）包封到OCD NP中，获得了一种ROS响应性纳米疗法CPT-11/OCD NP，并通过[具体实验3]和[具体实验4]研究评估了其抗肿瘤活性。还对CPT-11/OCD NP在小鼠中进行了初步安全性研究。：OCD NP显著减轻了不同诱导性结肠炎细胞和小鼠中的氧化应激并抑制了炎症反应。CPT-11/OCD NP能够在肠道pH条件和高浓度ROS下选择性释放药物分子。在C26小鼠结肠癌细胞中，与游离CPT-11和无响应的CPT-11纳米疗法相比，这种纳米疗法显示出显著更高的抗肿瘤活性。相应地，口服给予CPT-11/OCD NP显著抑制了诱导性CAC小鼠的肿瘤发生和肿瘤生长。通过在炎症阶段与纳米载体OCD NP联合治疗，获得了更理想的治疗效果。此外，CPT-
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