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Biological activities of siRNA-loaded lanthanum phosphate nanoparticles on colorectal cancer
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-08-27 , DOI: 10.1016/j.jconrel.2020.08.027 Piao-Piao Li 1 , Yi Yan 1 , Hai-Tao Zhang 2 , Shi-He Cui 1 , Cheng-Han Wang 1 , Wei Wei 1 , Hong-Gang Qian 3 , Jian-Cheng Wang 1 , Qiang Zhang 1
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-08-27 , DOI: 10.1016/j.jconrel.2020.08.027 Piao-Piao Li 1 , Yi Yan 1 , Hai-Tao Zhang 2 , Shi-He Cui 1 , Cheng-Han Wang 1 , Wei Wei 1 , Hong-Gang Qian 3 , Jian-Cheng Wang 1 , Qiang Zhang 1
Affiliation
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Lanthanum can reduce absorption of phosphate by forming lanthanum phosphate complexes after oral administration of lanthanum carbonate tablets (FOSRENOL®) in patients. Based on the pH-responsive interaction of phosphate and lanthanum ions, the chitosan coated siRNA-loaded lanthanum phosphate nanoparticles (CS/LaP/siRNA NPs) were prepared for improving cancer treatment, in which polysaccharide chitosan was used as the outer shell to control the excessive growth of lanthanum phosphate complexes, and enable intestinal mucoadhesion. The CS/LaP/siEGFR NPs exhibited significant biological activities in human colorectal cancer HT-29 cells by the synergistic effects of siEGFRs and lanthanum ions, such as downregulation of EGFR and upregulation of miR-34a. Furthermore, significant tumor growth inhibition was observed in both transgenic C57BL/6-Apc/Nju cancer mouse model and AOM/DSS chemically induced orthotopic colorectal cancer mouse model after intestinal instillation administration of CS/LaP/siEGFR NPs. Therefore, the lanthanum-based siRNA delivery system would provide a potential and efficient strategy for the treatment of colorectal cancers.
中文翻译：
负载siRNA的磷酸镧纳米粒子对结直肠癌的生物学活性
患者口服碳酸镧片（FOSRENOL®）后，镧可以通过形成磷酸镧复合物来减少磷酸盐的吸收。基于磷酸盐和镧离子的pH响应性相互作用，制备了壳聚糖包覆的负载siRNA的磷酸镧纳米颗粒（CS/LaP/siRNA NPs）以改善癌症治疗，其中多糖壳聚糖用作外壳以控制磷酸镧络合物过度生长，并使肠粘膜粘附。通过siEGFR和镧离子的协同作用，CS/LaP/siEGFR NPs在人结直肠癌HT-29细胞中表现出显着的生物活性，例如下调EGFR和上调miR-34a。此外，在转基因C57BL/6-Apc/Nju癌症小鼠模型和AOM/DSS化学诱导的原位结直肠癌小鼠模型中，肠道灌注CS/LaP/siEGFR NPs后，观察到显着的肿瘤生长抑制。因此，基于镧的siRNA递送系统将为结直肠癌的治疗提供潜在且有效的策略。
更新日期：2020-08-27
中文翻译：
负载siRNA的磷酸镧纳米粒子对结直肠癌的生物学活性
患者口服碳酸镧片（FOSRENOL®）后，镧可以通过形成磷酸镧复合物来减少磷酸盐的吸收。基于磷酸盐和镧离子的pH响应性相互作用，制备了壳聚糖包覆的负载siRNA的磷酸镧纳米颗粒（CS/LaP/siRNA NPs）以改善癌症治疗，其中多糖壳聚糖用作外壳以控制磷酸镧络合物过度生长，并使肠粘膜粘附。通过siEGFR和镧离子的协同作用，CS/LaP/siEGFR NPs在人结直肠癌HT-29细胞中表现出显着的生物活性，例如下调EGFR和上调miR-34a。此外，在转基因C57BL/6-Apc/Nju癌症小鼠模型和AOM/DSS化学诱导的原位结直肠癌小鼠模型中，肠道灌注CS/LaP/siEGFR NPs后，观察到显着的肿瘤生长抑制。因此，基于镧的siRNA递送系统将为结直肠癌的治疗提供潜在且有效的策略。
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