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Low-Molecular-Weight Poly(ethylenimine) Nanogels Loaded with Ultrasmall Iron Oxide Nanoparticles for T1-Weighted MR Imaging-Guided Gene Therapy of Sarcoma
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-09 , DOI: 10.1021/acsami.1c04081 Yucheng Peng 1 , Yue Gao 1 , Chao Yang 1 , Rui Guo 1 , Xiangyang Shi 1 , Xueyan Cao 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-09 , DOI: 10.1021/acsami.1c04081 Yucheng Peng 1 , Yue Gao 1 , Chao Yang 1 , Rui Guo 1 , Xiangyang Shi 1 , Xueyan Cao 1
Affiliation
Cancer metastasis is still a major obstacle in clinical cancer therapy and a paramount cause of cancer deaths. Designing multifunctional nanoplatforms with an enhanced diagnostic sensitivity and anti-metastasis efficiency against tumors represents a major trend in current cancer management. Herein, we report the preparation of low-molecular-weight poly(ethylenimine) (PEI)-poly(ethylene glycol) (PEG) nanogels (NGs) loaded with transforming growth factor-β1 (TGF-β1) siRNA and ultrasmall iron oxide nanoparticles (Fe3O4 NPs) for gene therapy and T1-weighted magnetic resonance (MR) imaging of tumors and tumor metastasis in a mouse sarcoma model. In this work, ultrasmall Fe3O4 NPs stabilized by sodium citrate were first prepared and then mixed with PEI (800 Da) and PEG (400 Da)-diacrylate as a cross-linker to form Fe3O4/PEI-PEG NGs with an average size of 76.3 nm via an inverse microemulsion method. The developed hybrid NGs display good cytocompatibility and enhanced MR imaging performance (r1 relaxivity = 1.0346 mM–1 s–1). The Fe3O4/PEI-PEG NGs can be further used to compact TGF-β1 siRNA through electrostatic interaction and efficiently deliver siRNA to cancer cells and a tumor model to silence the TGF-β1 gene, which inhibits the growth and invasion of cancer cell in vitro significantly, as well as the growth of a subcutaneous sarcoma tumor model and lung metastasis in vivo. The designed hybrid NG-ultrasmall iron oxide NPs may be extended for the delivery of other drugs or genes for theranostics of different biological systems.
中文翻译:
载有超小氧化铁纳米颗粒的低分子量聚(乙烯亚胺)纳米凝胶用于 T1 加权 MR 成像引导的肉瘤基因治疗
癌症转移仍然是临床癌症治疗的主要障碍,也是癌症死亡的首要原因。设计具有增强的诊断敏感性和抗肿瘤转移效率的多功能纳米平台代表了当前癌症管理的主要趋势。在此,我们报告了负载转化生长因子-β1 (TGF-β1) siRNA 和超小氧化铁纳米颗粒的低分子量聚(乙烯亚胺)(PEI)-聚(乙二醇)(PEG)纳米凝胶(NGs)的制备(Fe 3 O 4 NPs) 用于小鼠肉瘤模型中肿瘤和肿瘤转移的基因治疗和T 1加权磁共振 (MR) 成像。在这项工作中,超小 Fe 3 O 4的NP稳定由柠檬酸钠是首先制备,然后用PEI(800道尔顿)和PEG(400道尔顿)-diacrylate混合作为交联剂,以形成的Fe 3 ö 4 / PEI-PEG NGS具有76.3纳米的平均尺寸通过一个反相微乳液法。开发的混合NGs显示出良好的细胞相容性和增强的MR成像性能(r 1弛豫率= 1.0346 mM –1 s –1)。Fe 3 O 4 /PEI-PEG NGs 可进一步通过静电相互作用压缩 TGF-β1 siRNA,有效地将 siRNA 递送至癌细胞和肿瘤模型以沉默 TGF-β1 基因,从而抑制癌症的生长和侵袭细胞在体外显着,以及皮下肉瘤肿瘤模型的生长和体内肺转移。设计的混合 NG-超小氧化铁 NPs 可以扩展用于其他药物或基因的递送,用于不同生物系统的治疗诊断。
更新日期:2021-06-23
中文翻译:
载有超小氧化铁纳米颗粒的低分子量聚(乙烯亚胺)纳米凝胶用于 T1 加权 MR 成像引导的肉瘤基因治疗
癌症转移仍然是临床癌症治疗的主要障碍,也是癌症死亡的首要原因。设计具有增强的诊断敏感性和抗肿瘤转移效率的多功能纳米平台代表了当前癌症管理的主要趋势。在此,我们报告了负载转化生长因子-β1 (TGF-β1) siRNA 和超小氧化铁纳米颗粒的低分子量聚(乙烯亚胺)(PEI)-聚(乙二醇)(PEG)纳米凝胶(NGs)的制备(Fe 3 O 4 NPs) 用于小鼠肉瘤模型中肿瘤和肿瘤转移的基因治疗和T 1加权磁共振 (MR) 成像。在这项工作中,超小 Fe 3 O 4的NP稳定由柠檬酸钠是首先制备,然后用PEI(800道尔顿)和PEG(400道尔顿)-diacrylate混合作为交联剂,以形成的Fe 3 ö 4 / PEI-PEG NGS具有76.3纳米的平均尺寸通过一个反相微乳液法。开发的混合NGs显示出良好的细胞相容性和增强的MR成像性能(r 1弛豫率= 1.0346 mM –1 s –1)。Fe 3 O 4 /PEI-PEG NGs 可进一步通过静电相互作用压缩 TGF-β1 siRNA,有效地将 siRNA 递送至癌细胞和肿瘤模型以沉默 TGF-β1 基因,从而抑制癌症的生长和侵袭细胞在体外显着,以及皮下肉瘤肿瘤模型的生长和体内肺转移。设计的混合 NG-超小氧化铁 NPs 可以扩展用于其他药物或基因的递送,用于不同生物系统的治疗诊断。