Two-Stage Size Decrease and Enhanced Photoacoustic Performance of Stimuli-Responsive Polymer-Gold Nanorod Assembly for Increased Tumor Penetration
Two-Stage Size Decrease and Enhanced Photoacoustic Performance of Stimuli-Responsive Polymer-Gold Nanorod Assembly for Increased Tumor Penetration
复制标题
刺激响应聚合物-金纳米棒组件的两阶段尺寸减小和增强的光声性能以增加肿瘤渗透
DOI：
10.1002/adfm.201806429
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发表时间：
2019-04-18
影响因子：
19
通讯作者：
Song, Jibin
中科院分区：
文献类型：
--
作者：
Liu, Tianji;Tong, Lingling;Song, Jibin
纳米药物在肿瘤细胞内的有效传递和释放是一种很有前景的实体肿瘤治疗平台。然而，多种生物屏障，特别是与肿瘤微环境相关的生物屏障，阻碍了这些治疗药物到达肿瘤细胞。本文报道了一个顺序的pH和还原响应聚合物和金纳米棒（AuNR）核-壳组装，通过两个阶段的尺寸减小和纳米平台的拆卸来克服这些障碍，以响应特定的肿瘤微环境。杂化纳米颗粒（NP）的肿瘤摄取率为14.2% ID g(-1)，分别是无反应的杂化纳米颗粒和小的AuNR@PEG的2倍和4倍。在肿瘤摄取杂化NPs后，被聚合还原反应性多柔比星（DOX）前药单体聚合物包裹的分解的超小aunr渗透到实体肿瘤中，并导致肿瘤细胞中局部DOX释放。光声效应（PA）在AuNR簇表面激活聚合物后呈线性增加，表明电磁场在AuNR组装中起着关键作用，这与理论计算结果一致。此外，混合NP可以作为一种有前途的深部组织PA和表面增强拉曼散射显像剂，用于实时体内生理行为和深部肿瘤穿透纳米治疗效果的研究。
A promising theranostic platform for solid tumors would deliver and release anticancer nanomedicine effectively in tumor cells. However, diverse biological barriers, especially related to the tumor microenvironment, impede these theranostic agents from reaching the tumor cell. Herein, a sequential pH and reduction-responsive polymer and gold nanorod (AuNR) core-shell assembly to overcome these barriers via a two-stage size decrease and disassembly of the nanoplatform responding to the specified tumor microenvironment are reported. The tumor uptake of the hybrid nanoparticle (NP) is 14.2% ID g(-1), which is two and four times higher than the noneresponsive hybrid NPs and small AuNR@PEG, respectively. After tumor uptake of the hybrid NPs, the disassembled ultrasmall AuNRs coated with a polymer of polymerized reduction-responsive doxorubicin (DOX) prodrug monomers penetrate into the solid tumor and lead to localized DOX release in the tumor cell. A linear increase in photoacustic (PA) effects from the PA activating polymer on an AuNR cluster surface indicates a critical role of electromagnetic fields in the AuNR assembly, which is consistent with the theoretical calculation results. Furthermore, the hybrid NP can serve as a promising deep-tissue PA and surface-enhanced Raman scattering imaging agent for real-time in vivo investigation of physiological behaviors and deep tumor penetrating nanotherapy effects.