Charge-reversal biodegradable MSNs for tumor synergetic chemo/ photothermal and visualized therapy
Charge-reversal biodegradable MSNs for tumor synergetic chemo/ photothermal and visualized therapy
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DOI：
10.1016/j.jconrel.2021.09.005
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发表时间：
2021-09-15
影响因子：
10.8
通讯作者：
Zeng, Xiaowei
中科院分区：
文献类型：
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作者：
Li, Zimu;Yang, Yao;Zeng, Xiaowei
鉴于介孔二氧化硅纳米颗粒（NPs）的生物降解困难，肿瘤部位的富集和渗透，以及治疗过程的实时监测，我们开发了一种负载甘露糖的介孔二氧化硅纳米颗粒（MSN-Man-DOX），并被聚多巴胺- gd3 + (PDA-Gd)金属酚网络包裹，并被聚（2-乙基-2-恶唑啉）（PEOz）修饰，构建了一种新型纳米药物MSN-Man-DOX@PDA-Gd-PEOz。体外评价了其ph响应电荷反转、光热、生物降解、药物释放和磁共振成像（MRI）性能。通过细胞实验研究了纳米平台的细胞摄取、肿瘤穿透、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体内MRI、器官分布、光热状况、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，通过化疗和光热疗法（PTT）与磁共振成像造影剂监测疾病功能的协同作用，可产生优异的治疗效果。而且治疗效果完成后MSN-Man-DOX@PDA-Gd-PEOz可生物降解，具有良好的临床应用前景。
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+ (PDA-Gd) 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 antitumor 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.