State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University , Shanghai 200433, People's Republic of China.
ACS Appl Mater Interfaces. 2018 Feb 7;10(5):4439-4449. doi: 10.1021/acsami.7b16999. Epub 2018 Jan 26.
The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated cellular apoptosis has achieved great progress. However, this kind of theraputic strategy still faces some challenges such as light, photosensitizer and oxygen (O) dependence. In this article, a ROS-mediated anticancer therapy independent of light, photosensitizer and oxygen was established based on a Fe-induced ROS-generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)-based polymer, which consisted of dopamine, indocyanine green, and polyethylene glycol side chain, was coated onto the surface of ART-loaded MSP. When the nanoparticles entered into cancer cells, a reaction of Fe-mediated cleavage of the endoperoxide bridge contained in ART occurred and subsequent a large amount of ROS was generated. Moreover, a NIR light was used to effectively increase the local temperature of tumor in virtue of the superior photothermal effects of MSP, which enabled us to accelerate the ROS generation and achieved an enhanced ROS yield. The newly developed nanodrug system displayed a high level of intracellular ROS generation, leading to the desired killing efficacy against malignant cells and solid tumor. This smart nanosystem holds great potential to overcome the existing barrier in PDT and opens a promising avenue for anticancer therapy.
基于活性氧（ROS）介导的细胞凋亡的抗癌疗法已经取得了很大进展。然而，这种治疗策略仍然面临一些挑战，如光、光敏剂和氧气（O）的依赖性。本文基于 Fe 诱导的 ROS 生成纳米系统，建立了一种不依赖光、光敏剂和氧气的 ROS 介导的抗癌疗法。首先，通过纳米沉积法将青蒿素（ART）负载在多孔磁性超粒子（MSP）上。然后，将基于聚（天冬氨酸）的聚合物，其包含多巴胺、吲哚菁绿和聚乙二醇侧链，涂覆在载有 ART 的 MSP 表面。当纳米颗粒进入癌细胞时，ART 中包含的内过氧化物桥的 Fe 介导的裂解反应发生，随后产生大量的 ROS。此外，近红外光（NIR）被用于有效地增加肿瘤的局部温度，这得益于 MSP 的优越光热效应，从而加速了 ROS 的生成，并实现了增强的 ROS 产量。新开发的纳米药物系统显示出高水平的细胞内 ROS 生成，导致对恶性细胞和实体瘤的所需杀伤效果。这种智能纳米系统有望克服 PDT 中现有的障碍，并为癌症治疗开辟了有前途的途径。
