Size-Controllable DNA Origami-Stacked Gold Nanoparticles for Deep Tumor-Penetrating Therapy.
Size-Controllable DNA Origami-Stacked Gold Nanoparticles for Deep Tumor-Penetrating Therapy.
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DOI：
10.1021/acsami.2c05750
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发表时间：
2022-08
影响因子：
9.5
通讯作者：
Dening Gu;Yanqi Qiao;Hongli Fu;Hongjie Zhao;Xinmin Yue;Shuo Wang;Yongmei Yin;Rimo Xi;
中科院分区：
文献类型：
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作者：
Dening Gu;Yanqi Qiao;Hongli Fu;Hongjie Zhao;Xinmin Yue;Shuo Wang;Yongmei Yin;Rimo Xi;
随着纳米技术的迅速发展，研究人员设计了各种智能纳米给药系统，以增强抗癌药物的肿瘤靶向性。然而，增加的肿瘤积聚并不表明在肿瘤组织中的更深的渗透，否则核心区域中的肿瘤细胞不能被充分杀死。在此，我们开发了一种用于深度穿透癌症治疗的尺寸可控的纳米颗粒系统，该系统将随着从正常组织到肿瘤微环境和细胞内区域的pH值的降低而可编程地分解。整合的纳米颗粒由金纳米颗粒（GNP，约30 nm）和负载有多柔比星（DOX）的四面体DNA纳米结构（TDN，约25 nm）组成。最初，纳米颗粒保持较大的尺寸（约100 nm），通过增强的渗透性和滞留效应在肿瘤中积累。在肿瘤微环境的pH约为6.5时，随着DNA序列的连接转化为三链体结构，TDNs从GNP分离并深入渗透到肿瘤细胞中，然后内化到细胞中。最后，在pH 5.0的酸性溶酶体中，TDNs通过形成i基序结构释放DOX。因此，这种纳米智能递送系统显示出有效的深度渗透到肿瘤核心，具有良好的抗肿瘤功效和令人满意的生物相容性，并为开发用于抗癌治疗的智能纳米系统提供了新的见解。
With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle is composed of a gold nanoparticle (GNP, ∼30 nm) and a tetrahedral DNA nanostructure (TDN, ∼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (∼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory biocompatibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.