The role of size in PEGylated liposomal doxorubicin biodistribution and anti-tumour activity

IF 3.8 4区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS
Saba Dadpour, Amin Mehrabian, Mahdieh Arabsalmani, Elaheh Mirhadi, Anis Askarizadeh, Mohammad Mashreghi, Mahmoud Reza Jaafari
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引用次数: 7

Abstract

The size of nanoliposome-encapsulated drugs significantly affects their therapeutic efficacy, biodistribution, targeting ability, and toxicity profile for the cancer treatment. In the present study, the biodistribution and anti-tumoral activity of PEGylated liposomal Doxorubicin (PLD) formulations with different sizes were investigated. First, 100, 200, and 400 nm PLDs were prepared by remote loading procedure and characterised for their size, zeta potential, encapsulation efficacy, and release properties. Then, in vitro cellular uptake and cytotoxicity were studied by flow cytometry and MTT assay, and compared with commercially available PLD Caelyx®. In vivo studies were applied on BALB/c mice bearing C26 colon carcinoma. The cytotoxicity and cellular uptake tests did not demonstrate any statistically significant differences between PLDs. The biodistribution results showed that Caelyx® and 100 nm liposomal formulations had the most doxorubicin (Dox) accumulation in the tumour tissue and, as a result, considerably suppressed tumour growth compared with 200 and 400 nm PLDs. In contrast, larger nanoparticles (200 and 400 nm formulations) had more accumulation in the liver and spleen. This study revealed that 90 nm Caelyx® biodistribution profile led to the stronger anti-tumour activity of the drug and hence significant survival extension, and showed the importance of vesicle size in the targeting of nanoparticles to the tumour microenvironment for the treatment of cancer.

Abstract Image

大小在聚乙二醇化脂质体阿霉素生物分布和抗肿瘤活性中的作用。
纳米脂质体包封药物的大小显著影响其治疗癌症的疗效、生物分布、靶向能力和毒性特征。在本研究中,研究了不同大小的聚乙二醇化脂质体阿霉素(PLD)的生物分布和抗肿瘤活性。首先,通过远程加载工艺制备了100nm、200nm和400nm的pld,并对其尺寸、zeta电位、封装效率和释放性能进行了表征。然后,通过流式细胞术和MTT法研究其体外细胞摄取和细胞毒性,并与市售PLD Caelyx®进行比较。体内研究应用于携带C26结肠癌的BALB/c小鼠。细胞毒性和细胞摄取试验未显示pld之间有统计学上的显著差异。生物分布结果显示,Caelyx®和100 nm脂质体制剂在肿瘤组织中具有最多的阿霉素(Dox)积累,因此与200和400 nm脂质体相比,可显著抑制肿瘤生长。相比之下,更大的纳米颗粒(200和400纳米配方)在肝脏和脾脏中积累更多。本研究表明,90 nm的Caelyx®生物分布曲线使药物具有更强的抗肿瘤活性,从而显着延长生存期,并显示了囊泡大小在将纳米颗粒靶向肿瘤微环境以治疗癌症方面的重要性。
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来源期刊
IET nanobiotechnology
IET nanobiotechnology 工程技术-纳米科技
CiteScore
6.20
自引率
4.30%
发文量
34
审稿时长
1 months
期刊介绍: Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf
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