Multifunctional siRNA-Laden Hybrid Nanoplatform for Noninvasive PA/IR Dual-Modal Imaging-Guided Enhanced Photogenetherapy
Multifunctional siRNA-Laden Hybrid Nanoplatform for Noninvasive PA/IR Dual-Modal Imaging-Guided Enhanced Photogenetherapy
复制标题
用于无创 PA/IR 双模态成像引导增强光基因治疗的多功能 siRNA 混合纳米平台
DOI：
10.1021/acsami.0c04533
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发表时间：
2020-05-20
影响因子：
9.5
通讯作者：
Wang, Fuan
中科院分区：
文献类型：
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作者：
Feng, Jie;Yu, Wenqian;Wang, Fuan
小干扰RNA（siRNA）诱导的基因治疗被认为是有效治疗癌症的一种有前景的途径，但易酶降解、转染效率差、非特异性生物分布和不受控制的释放阻碍了其广泛的临床应用。沸石咪唑酯框架 8 (ZIF-8) 已成为有前途的药物载体，但尚未对可编程 siRNA 递送进行深入探索。在此，我们报告了一种多功能 PDA-ZIF-8 (PZ) 纳米平台，用于通过光声 (PA)/近红外 (IR) 双模态成像的无创引导，结合光热疗法 (PTT) 和基因疗法 (GT) 来递送 siRNA。巧妙的 PZ 纳米载体介导治疗性 siRNA 的肿瘤特异性积累，而不会发生不需要的降解和预泄漏。 pH 响应型 ZIF-8 在酸性肿瘤微环境中分解，同时释放 siRNA 有效负载，用于在基因沉默治疗中裂解靶标 mRNA。同时，聚多巴胺纳米颗粒（PDA）可以同时充当强大的无创PA/IR成像造影剂和用于诊断引导光基因治疗的多功能光热剂。系统的体外和体内实验探索表明，与相应的PTT或GT单一疗法相比，我们的PDAs-siRNA-ZIF-8（PSZ）可以大大提高治疗效率。这项工作对于推动更智能的诊断和治疗策略的发展具有巨大的潜力，从而在不久的将来提供有前景的智能纳米药物。
Small interfering RNA (siRNA)-induced gene therapy has been recognized as a promising avenue for effective cancer treatment, while easy enzymatic degradation, poor transfection efficiency, nonspecific biodistribution, and uncontrolled release hinder its extensive clinical applications. Zeolitic imidazolate frameworks-8 (ZIF-8) have emerged as promising drug carriers without an in-depth exploration in programmable siRNA delivery. Herein, we report a multifunctional PDAs-ZIF-8 (PZ) nanoplatform for delivering siRNA with combined photothermal therapy (PTT) and gene therapy (GT) via the noninvasive guidance of photoacoustic (PA)/near-infrared (IR) dual-modal imaging. The ingenious PZ nanocarriers mediated the tumor-specific accumulation of therapeutic siRNA without undesired degradation and preleakage. The pH-responsive ZIF-8 decomposed in an acidic tumor microenvironment that was accompanied by the release of siRNA payloads for cleaving target mRNA in gene silencing therapy. Meanwhile, the polydopamine nanoparticles (PDAs) could simultaneously serve as a powerful noninvasive PA/IR imaging contrast agent and versatile photothermal agent for diagnosis-guided photogenetherapy. The systematic in vitro and in vivo experimental explorations demonstrated that our PDAs-siRNA-ZIF-8 (PSZ) could greatly enhance the therapeutic efficiency as compared with the corresponding PTT or GT monotherapy. This work holds great potential to advance the development of more intelligent diagnosis and therapeutic strategies, thus supplying promising smart nanomedicines in the near future.