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Charge-reversal biodegradable MSNs for tumor synergetic chemo/photothermal and visualized therapy
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.jconrel.2021.09.005
Zimu Li 1 , Yao Yang 1 , Huaxuan Wei 1 , Xiaoting Shan 1 , Xuanzhi Wang 1 , Meitong Ou 1 , Qingyun Liu 1 , Nansha Gao 1 , Hongzhong Chen 1 , Lin Mei 2 , Xiaowei Zeng 1
Affiliation  

Given the difficulties of biodegradation of mesoporous silica nanoparticles (NPs), enrichment and penetration of tumor sites, and real-time monitoring of the treatment process, we developed a kind of mannose-doping doxorubicin-loading mesoporous silica nanoparticle (MSN-Man-DOX) and coated by polydopamine-Gd3+ (PDAsingle bondGd) metal-phenolic networks, as well as modified by poly (2-Ethyl-2-Oxazoline) (PEOz), constructing a novel nanomedicine MSN-Man-DOX@PDA-Gd-PEOz. Its pH-responsive charge reversal, photothermal, biodegradation, drug release, and magnetic resonance imaging (MRI) properties were evaluated in vitro. Cellular uptake, tumor penetration, lysosomal escape properties, as well as cell safety and toxicity of the nanoplatform were investigated through cell experiments. Finally, the MRI, organ distribution, photothermal condition, and comprehensive anti-tumor therapy in vivo were evaluated comprehensively through animal experiments. Research results showed that MSN-Man-DOX@PDA-Gd-PEOz had outstanding tumor enrichment and penetration abilities, which can produce excellent treatment effects through the synergistic effect of chemotherapy and photothermal therapy (PTT) with the function of magnetic resonance imaging contrast agent for disease monitoring. Besides, after finishing the therapeutic effect MSN-Man-DOX@PDA-Gd-PEOz can be biodegraded, so it had a good prospect of clinical application.



中文翻译:

用于肿瘤协同化学/光热和可视化治疗的电荷逆转可生物降解 MSN

鉴于介孔二氧化硅纳米粒子 (NPs) 的生物降解、肿瘤部位的富集和渗透以及治疗过程的实时监测等困难,我们开发了一种甘露糖掺杂阿霉素负载的介孔二氧化硅纳米粒子 (MSN-Man-DOX ) 并由聚多巴胺-Gd 3+ (PDA 单键Gd) 金属-酚类网络包覆,并由聚 (2-乙基-2-恶唑啉) (PEOz) 修饰,构建了新型纳米药物 MSN-Man-DOX@PDA-Gd -PEOz。在体外评估其 pH 响应性电荷反转、光热、生物降解、药物释放和磁共振成像 (MRI) 特性. 通过细胞实验研究了纳米平台的细胞摄取、肿瘤渗透、溶酶体逃逸特性以及细胞安全性和毒性。最后,通过动物实验对MRI、器官分布、光热条件和体内综合抗肿瘤治疗进行综合评价。研究结果表明,MSN-Man-DOX@PDA-Gd-PEOz具有突出的肿瘤富集和穿透能力,可通过化疗和光热疗法(PTT)的协同作用以及磁共振成像造影剂的作用产生优异的治疗效果用于疾病监测。此外,MSN-Man-DOX@PDA-Gd-PEOz治疗完成后可生物降解,具有良好的临床应用前景。

更新日期:2021-09-15
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