Tandem activated photodynamic and chemotherapy: Using pH-Sensitive nanosystems to realize different tumour distributions of photosensitizer/prodrug for amplified combination therapy
Tandem activated photodynamic and chemotherapy: Using pH-Sensitive nanosystems to realize different tumour distributions of photosensitizer/prodrug for amplified combination therapy
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DOI：
10.1016/j.biomaterials.2019.119393
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发表时间：
2019-10-01
期刊：
影响因子：
14
通讯作者：
Huang, Wei
中科院分区：
文献类型：
--
作者：
Ji, Yu;Lu, Feng;Huang, Wei
光动力疗法（PDT）与缺氧激活前药相结合来克服缺氧环境最近已被探索为一种有前途的癌症治疗临床方式。然而，将这两种治疗剂一起递送到具有许多生物屏障的不同肿瘤区域仍然是一个相当大的挑战。在此，我们使用基于半导体聚电解质的两性离子光敏剂（PENS）来修饰上转换纳米颗粒（NP）的表面并制备近红外（NIR）光响应PDT制剂（UCNP@PFNS）。将 pH 敏感的 Mn-Ca-3(PO4)(2) (MnCaP) 层进一步涂覆到 UCNP@PFNS 上，其中掺入缺氧激活的前药 AQ4N。最终的纳米复合材料直径为 73 nm，在血液中具有高稳定性，并且在肿瘤中具有显着增强的渗透性和保留（EPR）效果。重要的是，当这些纳米颗粒到达肿瘤部位时，酸性肿瘤微环境（pH 6.5-6.8）分解MnCaP层，释放UCNP@PFNS（30 nm）和AQ4N。 UCNP@PFNS和AQ4N相对较小的尺寸满足了肿瘤中不同的分布要求，取得了较高的治疗效果，抑制率高达83%。此外，CaP分解过程中会释放Mn2+离子，导致肿瘤部位的磁共振（MR）信号显着增加。总的来说，我们报道了一种由 MRI 和荧光成像引导的纳米粒子，具有 PDT 和化疗的串联活性模式，这对于未来的临床诊断和治疗具有广阔的前景。
Photodynamic therapy (PDT) combined with hypoxia-activated prodrugs to overcome hypoxia environment has been recently explored as a promising clinical modality for cancer therapy. Nevertheless, delivering these two therapeutic agents together to different tumour areas that possess a number of biological barriers remains a considerable challenge. Herein, we used the semiconducting polyelectrolyte-based zwitterionic photosensitizer (PENS) to modify the surface of upconversion nanoparticles (NPs) and prepare near-infrared (NIR) light-responsive PDT agents (UCNP@PFNS). A pH-sensitive Mn-Ca-3(PO4)(2) (MnCaP) layer was further coated onto UCNP@PFNS with the hypoxia-activated prodrug AQ4N incorporated inside. The final nanocomposites exhibited a diameter of 73 nm with high stability in the blood and a remarkably enhanced permeability and retention (EPR) effect in tumours. Importantly, when these nanoparticles reached the tumour site, the acidic tumour microenvironment (pH 6.5-6.8) decomposed the MnCaP layer, releasing both UCNP@PFNS (30 nm) and AQ4N. The relatively small size of UCNP@PFNS and AQ4N satisfied the different distribution requirements in tumour and achieved a high therapeutic effect, thereby reaching an inhibition rate of as high as 83%. In addition, Mn2+ ions can be released during the decomposition of CaP, leading to a significantly increased magnetic resonance (MR) signal in the tumour site. Overall, we report a nanoparticle guided by MRI and fluorescence imaging possesses of tandem active pattern of PDT and chemotherapy, which is promising for future clinical diagnosis and treatment.