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树枝状聚合物修饰的纳米凝胶:用于卵巢癌生物分布和化疗的高效纳米载体。

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution and chemotherapy of ovarian carcinoma.

作者信息

Li Xin, Ouyang Zhijun, Li Helin, Hu Chaolei, Saha Pabitra, Xing Lingxi, Shi Xiangyang, Pich Andrij

机构信息

DWI-Leibniz-Institute for Interactive Materials e.V, 52056, Aachen, Germany.

Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, 52074, Aachen, Germany.

出版信息

Bioact Mater. 2021 Mar 13;6(10):3244-3253. doi: 10.1016/j.bioactmat.2021.02.031. eCollection 2021 Oct.

DOI:10.1016/j.bioactmat.2021.02.031
PMID:33778202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7970313/
Abstract

Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy. Here, the PAMAM dendrimer decorated PVCL-GMA nanogels (NGs) were developed for favorable biodistribution and enhanced antitumor efficacy of ovarian carcinoma. By an ingenious design, the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized precipitation polymerization. After G2 dendrimer decoration, the overall charge is changed from neutral to positive, and the NGs-G2 display the whole charge nature of positively charged corona and neutral core. Importantly, the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery . As a consequence of this alteration, the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation, enhanced tumor uptake, and promoted drug release, resulting in the significantly augmented antitumor efficacy with low side effects. Remarkably, this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake. Moreover, the NGs-G2 also displayed thermal/pH dual-responsive behaviors, excellent biocompatibility, improved cellular uptake, and stimuli-responsive drug release. Encouragingly, this work demonstrates a novel insight into the strategy for optimizing design, improving biodistribution and enhancing theranostic efficacy of nanocarriers.

摘要

纳米医学通过精确诊断和高效治疗彻底改变了疾病的诊疗方式。在此,制备了聚酰胺-胺(PAMAM)树枝状大分子修饰的聚氯乙烯-甲基丙烯酸缩水甘油酯(PVCL-GMA)纳米凝胶(NGs),以实现卵巢癌良好的生物分布并增强其抗肿瘤疗效。通过巧妙设计,采用沉淀聚合法合成了具有独特结构(富含甲基丙烯酸缩水甘油酯(GMA)的区域位于表面)的纳米凝胶。在修饰G2树枝状大分子后,整体电荷从中性变为正性,NGs-G2呈现出带正电晕层和中性核的整体电荷性质。重要的是,NGs-G2独特的结构和电荷转换对生物分布和药物递送有深远影响。由于这种改变,作为纳米载体的NGs-G2呈现出减少肝脏蓄积、增强肿瘤摄取和促进药物释放的高度理想生物分布,从而显著增强抗肿瘤疗效且副作用低。值得注意的是,这一发现与一些报道的带正电荷纳米载体优先被肝脏摄取的研究结果相反。此外,NGs-G2还表现出热/ pH双重响应行为、优异的生物相容性、改善的细胞摄取和刺激响应性药物释放。令人鼓舞的是,这项工作为优化纳米载体设计、改善生物分布和增强诊疗效果的策略提供了新的见解。

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