EGFR-targeted hybrid lipid nanoparticles for chemo-photothermal therapy against colorectal cancer cells

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2023-03-01 DOI:10.1016/j.chemphyslip.2023.105280

Fang Fang , Xinming Zhang , Jin Tang , Yu Wang , Jinchen Xu , Yu Sun

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引用次数: 2

Abstract

Antibody-functionalized targeted nanocarriers have shown great–potential for minimizing the chemoresistance and systemic toxicity of cancer chemotherapies. The combination of chemotherapy and photothermal therapy has great potential in improving therapeutic effect. However, cetuximab-modified nanoparticles based lipids for chemo-phototherapy of EGFR overexpressing colorectal carcinoma (CRC) have seldom been investigated. Hence, this study aimed to fabricate cetuximab-conjugated and near infrared (NIR) light-responsive hybrid lipid-polymer nanoparticles (abbreviated as Cet-CINPs) for targeted delivery of irinotecan. Cet-CINPs were prepared with copolymer PLGA and various lipids DSPE-PEG, DSPE-PEG-Mal, lecithin as carriers. Cetuximab was conjugated on the surface of nanoparticles to achieve targeting anti-tumor efficacy. Cet-CINPs were characterized in terms of morphology (spherical), size (119 nm), charge (−27.2 mV), drug entrapment efficiency (43.27 %), and antibody conjugation efficiency (70.87 %). Cet-CINPs showed preferable photothermal response, pH/NIR-triggered drug release behavior, enhanced cellular uptake and ROS level compared with free ICG and CINPs. Meanwhile, in vitro cytotoxicity assay showed that Cet-CINPs with NIR irradiation had a higher cytotoxicity against Lovo cells than non-targeted or non-NIR activated nanoparticles. The IC₅₀ values of Cet-CINPs with NIR irradiation was 22.84 ± 1.11 μM for 24 h and 5.01 ± 1.06 μM for 48 h, respectively. These investigations demonstrate that Cet-CINPs with good tumor-targeting ability and enhanced antitumor activity, are a promising multifunctional nanoplatform for CRC therapy.

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靶向egfr的杂化脂质纳米颗粒用于化疗-光热治疗结直肠癌细胞

抗体功能化的靶向纳米载体在减少癌症化疗的化疗耐药和全身毒性方面显示出巨大的潜力。化疗与光热联合治疗在提高治疗效果方面具有很大的潜力。然而，西妥昔单抗修饰的纳米脂质用于EGFR过表达结直肠癌(CRC)的化学光疗的研究很少。因此，本研究旨在制备西妥昔单抗共轭的近红外(NIR)光响应的混合脂质聚合物纳米颗粒(简称Cet-CINPs)，用于靶向递送伊立替康。以共聚物PLGA和各种脂质(DSPE-PEG、DSPE-PEG- mal、卵磷脂)为载体制备了Cet-CINPs。将西妥昔单抗偶联在纳米颗粒表面，实现靶向抗肿瘤作用。Cet-CINPs的形貌(球形)、尺寸(119 nm)、电荷(- 27.2 mV)、药物包封效率(43.27%)和抗体偶联效率(70.87%)均得到表征。与游离ICG和CINPs相比，Cet-CINPs表现出更好的光热响应、pH/ nir触发的药物释放行为、增强的细胞摄取和ROS水平。同时，体外细胞毒性实验表明，近红外照射的Cet-CINPs对Lovo细胞的细胞毒性高于非靶向或非近红外激活的纳米颗粒。Cet-CINPs的IC50值分别为22.84±1.11 μM (24 h)和5.01±1.06 μM (48 h)。这些研究表明Cet-CINPs具有良好的肿瘤靶向能力和增强的抗肿瘤活性，是一种很有前景的多功能CRC治疗纳米平台。

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.