Auto-fluorescent polymer nanotheranostics for self-monitoring of cancer therapy via triple-collaborative strategy
Auto-fluorescent polymer nanotheranostics for self-monitoring of cancer therapy via triple-collaborative strategy
复制标题
自体荧光聚合物纳米治疗学通过三重协作策略自我监测癌症治疗
DOI：
10.1016/j.biomaterials.2018.12.021
复制
发表时间：
2019-02-01
期刊：
影响因子：
14
通讯作者：
Wu, Yan
中科院分区：
文献类型：
--
作者：
Shao, Leihou;Li, Qun;Wu, Yan
血管生成的异常调节提供了充足的氧气和营养物质，加剧了肿瘤的进展和转移。考虑到癌症的这一标志，本文报道了一种通过自荧光聚合物纳米治疗剂的自我监测和三重协作治疗系统，其可以通过结合抗血管生成、RNA干扰和光热治疗（PTT）的益处来同时抑制血管生成和肿瘤细胞生长。带正电荷的两亲性聚合物聚乙烯亚胺-聚乳酸（PEI-PLA）可同时负载疏水性抗血管生成剂考布他汀A4（CA 4）、近红外染料IR 825和吸附带负电荷的热休克蛋白70（HSP 70）抑制剂（siRNA），构建自监测纳米治疗诊断剂（NPICS）。NPICS可有效抑制HSP 70的表达，降低其对IR 825介导的PTT的耐受性，从而增强光细胞毒性。在异种移植小鼠肿瘤模型中，NPICS显示出抑制肿瘤血管生成的效果，并且还显示出与NIR激光照射高度协同的抗癌功效。值得注意的是，基于其固有的自发荧光，PEI-PLA不仅可作为药物载体，还可作为自我监测器，通过荧光成像实时跟踪NPICS的生物分布和肿瘤蓄积。此外，IR 825赋予了NPICS作为光声（PA）剂用于体内PA成像的可能性。这种纳米平台在癌症治疗诊断学中显示出巨大的潜力。
Aberrant regulation of angiogenesis supply sufficient oxygen and nutrients to exacerbate tumor progression and metastasis. Taking this hallmark of cancer into account, reported here is a self-monitoring and triple-collaborative therapy system by auto-fluorescent polymer nanotheranostics which could be concurrently against angiogenesis and tumor cell growth by combining the benefits of anti-angiogenesis, RNA interfere and photo thermal therapy (PTT). Auto-fluorescent amphiphilic polymer polyethyleneimine-polylactide (PEI-PLA) with positive charge can simultaneously load hydrophobic antiangiogenesis agent combretastatin A4 (CA4), NIR dye IR825 and absorb negatively charged heat shock protein 70 (HSP70) inhibitor (siRNA against HSP70) to construct self-monitoring nanotheranostics (NPICS). NPICS can effectively restrain the expression of HSP70 to reduce their endurance to the IR825-mediated PTT, leading to an enhanced photocytotoxicity. In a xenograft mouse tumor model, NPICS show an effect of inhibition of tumor angiogenesis and also display a highly synergistic anticancer efficacy with NIR laser irradiation. Significantly, based on its inherent auto-fluorescence, PEI-PLA not only serves as the drug carrier, but also as the self-monitor to real-time track NPICS biodistribution and tumor accumulation via fluorescence imaging. Moreover, IR825 endows NPICS could also be used as photoacoustic (PA) agents for in vivo PA imaging. This nanoplatform shows enormous potentials in cancer theranostics.