Neutrophil-Mediated Delivery Platforms for Synergistic Chemo-Immunotherapy of Non-Small-Cell Lung Cancer Therapy

IF 9.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-09-16 DOI:10.1021/acs.nanolett.5c04210

Rongze Sun, , , Yunshuang Jiao, , , Jicong Chen, , , Xiang Pang, , , Beilin Xue, , , Jiaqi Yao, , , Guanpeng Li, , , Yue Zhang, , , Jie Yang*, , and , Lesheng Teng*,

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Abstract

Traditional nanocarriers possess good therapeutic efficacy in the treatment of non-small-cell lung cancer (NSCLC), but usually suffer from high immunogenicity, poor biosafety, and low targeting. In this work, a neutrophil-mediated delivery platform constructed from neutrophils (NEs) and paclitaxel/transforming growth factor-β (TGF-β) siRNA loaded cationic liposome, namely, siTGFβ-PLP-NEs, is fabricated for the combination therapy of NSCLC via synergistic chemo-immunotherapy. siTGFβ-PLP-NEs can be targeted to the tumor site and effectively release paclitaxel and siTGFβ, which is conducive to simultaneously inhibiting the proliferation of tumor cells and the expression of TGF-β. The experimental results demonstrate that siTGFβ-PLP-NEs can prevent the transition of tumor-associated NEs from an anti-tumor (N1) phenotype to a pro-tumor (N2) phenotype, enhance CD8⁺ T cell infiltration, and reduce regulatory T cell (Treg) infiltration, which provides a great promising combination therapy option to use neutrophil-mediated systems as a general-purpose delivery platform for the treatment of NSCLC.

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非小细胞肺癌协同化疗免疫治疗的中性粒细胞介导递送平台。

传统纳米载体在治疗非小细胞肺癌（NSCLC）中具有良好的疗效，但通常存在免疫原性高、生物安全性差、靶向性低等问题。本研究以中性粒细胞（NEs）和载紫杉醇/转化生长因子-β (TGF-β) siRNA的阳离子脂质体siTGFβ-PLP-NEs为载体，构建中性粒细胞介导的递送平台，通过协同化疗-免疫治疗联合治疗NSCLC。siTGFβ- plp - nes可靶向肿瘤部位，有效释放紫杉醇和siTGFβ，有利于同时抑制肿瘤细胞的增殖和TGF-β的表达。实验结果表明，siTGFβ-PLP-NEs可以阻止肿瘤相关NEs从抗肿瘤（N1）表型向促肿瘤（N2）表型转变，增强CD8+ T细胞浸润，减少调节性T细胞（Treg）浸润，这为利用中性粒细胞介导的系统作为治疗非小细胞肺癌的通用递送平台提供了一个很有前景的联合治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.