Zwitterionic Polysulfamide Drug Nanogels with Microwave Augmented Tumor Accumulation and On-Demand Drug Release for Enhanced Cancer Therapy
Zwitterionic Polysulfamide Drug Nanogels with Microwave Augmented Tumor Accumulation and On-Demand Drug Release for Enhanced Cancer Therapy
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两性离子聚磺酰胺药物纳米凝胶具有微波增强肿瘤积累和按需药物释放的能力，以增强癌症治疗
DOI：
10.1002/adfm.202001832
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发表时间：
2020-06-01
影响因子：
19
通讯作者：
Lu, Ligong
中科院分区：
文献类型：
--
作者：
Peng, Shaojun;Wang, Hao;Lu, Ligong
两性离子聚合物是一类在活体中具有长时间血液循环的生物材料。尽管对它们的可降解性进行了广泛的研究，但对可以通过温和的外部信号改变其性质的响应性两性离子聚合物的探索很少。本文中，开发了基于磺酰胺的两性离子单体并用于合成一系列基于聚磺酰胺的（聚（2-（（2-（甲基丙烯酰氧基）乙基）二甲基铵基）乙酰基）（苯磺酰基）酰胺（PMEDAPA））纳米凝胶，作为用于有效癌症治疗的药物载体。PMEDAPA纳米凝胶被证明表现出延长的血液循环而不诱导加速的血液清除现象。有趣的是，PMEDAPA纳米凝胶可以通过调节交联剂的程度来敏感地响应高温。经转铁蛋白（Tf）修饰后的纳米凝胶（PMEDAPA-Tf）在常温下实现屏蔽的肿瘤靶向，而在高温下表现出恢复的肿瘤靶向，导致增强的肿瘤积聚。同时，PMEDAPA-Tf纳米凝胶在三维肿瘤球体中显示出上级的渗透能力，并且与常温相比，在高温下药物释放更快。与温和的微波加热（约41摄氏度）相结合，载药PMEDAPA-Tf纳米凝胶在人源化正交异性肝癌模型中显示出明显的肿瘤抑制作用。因此，该研究提供了一种新型的高血压响应性两性离子纳米凝胶，其可以实现增强的肿瘤积累和按需药物释放，并辅助临床使用的微波加热用于癌症治疗。
Zwitterionic polymers demonstrate as a class of antifouling materials with long blood circulation in living subjects. Despite extensive research on their antifouling abilities, the responsive zwitterionic polymers that can change their properties by mild outside signals are poorly explored. Herein, a sulfamide-based zwitterionic monomer is developed and used to synthesize a series of polysulfamide-based (poly (2-((2-(methacryloyloxy)ethyl) dimethylammonio)acetyl) (phenylsulfonyl) amide (PMEDAPA)) nanogels as drug carriers for effective cancer therapy. PMEDAPA nanogels are proved to exhibit prolonged blood circulation without inducing the accelerated blood clearance phenomenon. Intriguingly, PMEDAPA nanogels can sensitively respond to hyperthermia by adjusting the crosslinker degree. After modified with transferrin (Tf), the nanogels (PMEDAPA-Tf) achieve shielded tumor targeting at normothermia, while exhibiting recovered tumor targeting at hyperthermia, leading to enhanced tumor accumulation. Meanwhile, PMEDAPA-Tf nanogels show superior penetration ability in 3D tumor spheroids and faster drug release at hyperthermia compared with that at normothermia. In combination with mild microwave heating (approximate to 41 degrees C), the drug-loaded PMEDAPA-Tf nanogels show a pronounced tumor inhibition effect in a humanized orthotropic liver cancer model. Therefore, the study provides a novel hyperthermia-responsive zwitterionic nanogel that can achieve augmented tumor accumulation and on-demand drug release assisted with clinically used microwave heating for cancer therapy.