Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering , China Agricultural University , 100083 Beijing , China.
State Key Laboratory of Biochemical Engineering , Institute of Process Engineering, Chinese Academy of Sciences , 100190 Beijing , China.
ACS Nano. 2019 Jan 22;13(1):260-273. doi: 10.1021/acsnano.8b05602. Epub 2019 Jan 9.
As a type of programmed cell death, ferroptosis is distinct from apoptosis. The combination of the two thus provides a promising modality with which to significantly improve anticancer treatment efficacy. To fully utilize this combination, we herein designed a nanolongan delivery system, which possessed a typical structure of one core (up-conversion nanoparticles, UCNP) in one gel particle (Fe cross-linked oxidized starch) with multiple on-demand conversions. The charge conversion of the nanolongan surface in a slightly acidic microenvironment enhanced circulation time for utilizing the enhanced permeability and retention effect, enabled efficient uptake by tumor cells, and induced subsequently lysosomal escape. As the core component, the UCNP with light conversion from near-infrared light to ultraviolet light circumvented the impediment of limited penetration depth and enabled the reduction of Fe to Fe. Accordingly, gel networks of nanolongan could be deconstructed due to this valence conversion, leading to the rapid release of Fe and doxorubicin (Dox). In this case, the Fenton reaction between Fe and intracellular HO generated potent reactive oxygen species for ferroptosis, while the co-released Dox penetrated into nucleus and induced apoptosis in a synergistic way. As a result, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that our nanolongan could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.
作为一种程序性细胞死亡方式，铁死亡有别于细胞凋亡。因此，两者的联合为显著提高抗癌治疗效果提供了一种很有前途的方法。为了充分利用这种联合作用，我们设计了一种纳米笼递药系统，它具有一个核心（上转换纳米粒子，UCNP）和一个凝胶颗粒（Fe 交联氧化淀粉）的典型结构，具有多种按需转化。纳米笼表面在微酸性环境中的电荷转换增强了循环时间，利用增强的渗透性和保留效应，使肿瘤细胞能够有效摄取，并诱导随后的溶酶体逃逸。作为核心成分，UCNP 将近红外光转换为紫外光，克服了穿透深度有限的障碍，并使 Fe 还原为 Fe。因此，纳米笼的凝胶网络由于这种价态转换而被破坏，导致 Fe 和阿霉素（Dox）的快速释放。在这种情况下，Fe 和细胞内 HO 之间的芬顿反应产生了强大的活性氧，用于铁死亡，而共同释放的 Dox 则穿透到细胞核中，并以协同的方式诱导细胞凋亡。结果，纳米笼表现出优异的抗癌治疗效果，同时具有较小的全身毒性，表明我们的纳米笼可以作为一种安全且高性能的铁死亡-细胞凋亡联合抗癌治疗平台。
