Graphene Oxide-Based Gene Modulation in Preferential Elimination of Lung Cancer Cells in a 3D Tumor Microenvironment Model

IF 4 Q2 ENGINEERING, BIOMEDICAL
Francesca Grilli, Sadman Sakib, Fabio Variola, Shan Zou
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Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, owing to its aggressive nature, late-stage diagnosis, and resistance to conventional therapies. Gene therapy offers a promising alternative by modulating specific genetic pathways to target cancer cells while sparing healthy ones. This study investigates the potential of chemically functionalized nanoscale graphene oxide (GO) as carriers for delivering therapeutic genes in a 3D tumor microenvironment (TME) model, incorporating lung cancer cells, human lung fibroblasts, and macrophages in a Matrigel-collagen matrix to mimic the structural properties and immune functions. These therapeutic genes, including small interfering RNAs and plasmid DNAs, regulate immune evasion markers (CD47 and CD24) and apoptosis-inducing proteins (ANT1). GO nanocarriers demonstrate preferential uptake in cancer cells, achieving transfection and gene modulation within the TME model. The individual delivery of genes downregulates cancer markers and induces ANT1 expression, resulting in lung cancer cell elimination. Co-delivery of CD47_siRNA and ANT1_pDNA produces synergistic efficacy, enhancing cancer cell elimination. These findings highlight the potential of GO-based gene therapies as a targeted and effective approach for lung cancer treatment, setting the stage for in vivo validation and clinical translation.

Abstract Image

基于氧化石墨烯的基因调控在三维肿瘤微环境模型中优先消除肺癌细胞
由于肺癌的侵袭性、晚期诊断和对常规治疗的耐药性,它仍然是世界范围内癌症相关死亡的主要原因。基因治疗提供了一个有希望的替代方案,通过调节特定的遗传途径来靶向癌细胞,同时保留健康的细胞。本研究探讨了化学功能化纳米级氧化石墨烯(GO)作为载体在三维肿瘤微环境(TME)模型中传递治疗基因的潜力,将肺癌细胞、人肺成纤维细胞和巨噬细胞纳入基质-胶原基质中,以模拟其结构特性和免疫功能。这些治疗性基因,包括小干扰rna和质粒dna,调节免疫逃避标记(CD47和CD24)和凋亡诱导蛋白(ANT1)。氧化石墨烯纳米载体在癌细胞中表现出优先摄取,在TME模型中实现转染和基因调节。基因的个体传递下调癌症标志物,诱导ANT1表达,导致肺癌细胞消除。CD47_siRNA和ANT1_pDNA共递送产生协同效应,增强癌细胞消除。这些发现突出了氧化石墨烯为基础的基因疗法作为一种靶向和有效的肺癌治疗方法的潜力,为体内验证和临床转化奠定了基础。
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来源期刊
Advanced Nanobiomed Research
Advanced Nanobiomed Research nanomedicine, bioengineering and biomaterials-
CiteScore
5.00
自引率
5.90%
发文量
87
审稿时长
21 weeks
期刊介绍: Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science. The scope of Advanced NanoBiomed Research will cover the following key subject areas: ▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging. ▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications. ▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture. ▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs. ▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization. ▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems. with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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