Dual Drug Delivery in Cancer Therapy Using Graphene Oxide-Based Nanoplatforms

IF 4 Q2 ENGINEERING, BIOMEDICAL
Ludmila Žárská, Eoin Moynihan, Arianna Rossi, Giada Bassi, Pavlína Balatková, Elisabetta Campodoni, Maria Galiana Cameo, Monica Montesi, Diego Montagner, Vaclav Ranc, Silvia Panseri
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Abstract

Many types of cancer are currently treated using a combination of chemotherapeutics, but unfortunately, this strategy is considerably limited by severe side effects. The current development of nanocarriers enables the use of multiple drugs anchored on one unique platform thus enhancing the initiated therapeutic effect and minimizing the possibility of drug resistance. In this context, a graphene-oxide-based 2D nanoplatform is developed, which is functionalized using highly branched polyethylene-glycol and a multimodal set of two drugs with various mechanisms of action, namely Pt-based complex (a Pt(IV) prodrugs based on cisplatin) and doxorubicin (DOX). We performed in vitro 2D screening on two cancer cell lines, namely glioblastoma and osteosarcoma, that were selected as models of two aggressive tumors that remain a massive challenge in oncology. The therapeutic effect of the developed nano-platform is higher at lower concentrations (15 μm of Pt-drug, 0.6 μm DOX) compared to the impact of the free drugs. This indicates a possible positive effect of the accumulation and transport of the drugs using this nanoplatform. Results obtained on 3D cell models using MG63 osteosarcoma cells uncovered an understandable lowered diffusion profile of the developed nanoplatforms, compared to the application of free drugs.

Abstract Image

利用基于氧化石墨烯的纳米平台在癌症治疗中实现双重给药
目前,许多类型的癌症都采用联合化疗的方法进行治疗,但遗憾的是,这种策略受到严重副作用的限制。目前开发的纳米载体可将多种药物锚定在一个独特的平台上,从而增强初始治疗效果,并最大限度地降低耐药性的可能性。在此背景下,我们开发了一种基于氧化石墨烯的二维纳米平台,该平台使用高支化聚乙二醇和两种具有不同作用机制的多模式药物(即铂基复合物(一种基于顺铂的铂(IV)原药)和多柔比星(DOX))进行功能化。我们在两种癌细胞系(即胶质母细胞瘤和骨肉瘤)上进行了体外二维筛选,这两种癌细胞系被选为两种侵袭性肿瘤的模型,它们仍然是肿瘤学中的巨大挑战。与游离药物的影响相比,所开发的纳米平台在较低浓度(15 μm Pt-药物,0.6 μm DOX)时的治疗效果更高。这表明使用这种纳米平台可能会对药物的积累和运输产生积极影响。利用 MG63 骨肉瘤细胞在三维细胞模型上获得的结果显示,与应用游离药物相比,所开发的纳米平台的扩散曲线明显降低。
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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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