Cascade-Responsive Upconversion Nanoplatform for Efficient Cell Nucleus Targeting and Boosted Photodynamic Tumor Therapy

IF 8.7 1区化学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Materials Letters Pub Date : 2024-10-31 DOI:10.1021/acsmaterialslett.4c01614

Bo Ling, Lijiao Yang, Chenchen Wang, Ling Dong, Yanyun Yang, Lun Wang, Jia Zhang and Yue Yuan*,

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Abstract

In order to increase tumor tissue penetration, enhance phototherapy efficiency, and reduce off-target toxicity, we have developed a dual-locked upconversion nanoplatform (UCNP@Glu-DMMA) with a charge-reversal property for tumor-specific, cell nucleus-penetrating photodynamic therapy (PDT). The negative charge on the surface of UCNP@Glu-DMMA ensured excellent stability during blood circulation and accumulation in the tumor microenvironment (TME). Subsequently, the combined effect of the acidic TME and γ-glutamyl transpeptidase (GGT) triggered a reversal of the surface charge from negative to positive. This reversal enhanced the uptake efficiency of UCNP, leading to an increased intracellular drug concentration, deep tumor penetration, and direct nucleus delivery for the localized release of reactive oxygen species, resulting in robust DNA damage. As a result, the efficacy of PDT was significantly and precisely boosted for GGT-overexpressed tumors. This work provides a promising strategy to engineer therapeutic platforms for managing a variety of diseases based on different biomarkers.

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级联反应上转换纳米平台高效细胞核靶向和光动力肿瘤治疗

为了增加肿瘤组织穿透，提高光疗效率，减少脱靶毒性，我们开发了一种双锁上转换纳米平台（UCNP@Glu-DMMA），具有用于肿瘤特异性，细胞核穿透光动力治疗（PDT）的电荷反转特性。UCNP@Glu-DMMA表面的负电荷保证了其在血液循环和肿瘤微环境（TME）积累过程中的良好稳定性。随后，酸性TME和γ-谷氨酰转肽酶（GGT）的共同作用引发了表面电荷由负向正的逆转。这种逆转增强了UCNP的摄取效率，导致细胞内药物浓度增加，深入肿瘤，并直接递送细胞核以局部释放活性氧，从而导致强大的DNA损伤。因此，PDT对ggt过表达肿瘤的疗效得到了显著而精确的提高。这项工作为设计基于不同生物标志物的各种疾病的治疗平台提供了一个有前途的策略。

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来源期刊

ACS Materials Letters MATERIALS SCIENCE, MULTIDISCIPLINARY-

CiteScore

14.60

自引率

3.50%

发文量

261

期刊介绍： ACS Materials Letters is a journal that publishes high-quality and urgent papers at the forefront of fundamental and applied research in the field of materials science. It aims to bridge the gap between materials and other disciplines such as chemistry, engineering, and biology. The journal encourages multidisciplinary and innovative research that addresses global challenges. Papers submitted to ACS Materials Letters should clearly demonstrate the need for rapid disclosure of key results. The journal is interested in various areas including the design, synthesis, characterization, and evaluation of emerging materials, understanding the relationships between structure, property, and performance, as well as developing materials for applications in energy, environment, biomedical, electronics, and catalysis. The journal has a 2-year impact factor of 11.4 and is dedicated to publishing transformative materials research with fast processing times. The editors and staff of ACS Materials Letters actively participate in major scientific conferences and engage closely with readers and authors. The journal also maintains an active presence on social media to provide authors with greater visibility.