Precision Nanomedicine: Lapatinib-Loaded Chitosan-Gold Nanoparticles Targeting LINC01615 for Lung Cancer Therapy.

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY AAPS Journal Pub Date : 2024-11-19 DOI:10.1208/s12248-024-00990-y
Hadi Rezaei Aghdam, Maryam Peymani, Ali Salehzadeh, Leila Rouhi, Atefeh Zarepour, Ali Zarrabi
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Abstract

Long non-coding RNAs (lncRNAs) play essential roles as oncogenic factors in cancer progression by influencing cell proliferation, apoptosis, and metastasis pathways. This study aims to investigate the expression changes of LINC01615 in prevalent cancers, explore its correlation with patient mortality rates, and introduce a novel therapeutic approach to reduce LINC01615 expression. Using The Cancer Genome Atlas (TCGA) data, the expression changes of LINC01615 in various cancers were analyzed, and its relationship with patient survival rates through Cox regression analysis weas assessed. Co-expressed pathways related to LINC01615 were identified via network analysis. Potential drugs to decrease LINC01615 expression were identified using the GSE38376 study. Besides, chitosan-coated nanoparticles were fabricated and functionalized with the identified drug, Lapatinib, to examine their effect on lung cancer cell lines and changes in LINC01615 expression. Our results indicated elevated LINC01615 expression in various common cancers, particularly in lung cancer, which was associated with poor prognosis in lung, breast, and kidney cancers. Co-expression network analysis suggested links to metastasis-related genes. Lapatinib, identified through GEO data, was found to modulate LINC01615 expression effectively. Chitosan-gold nanoparticles conjugated with Lapatinib significantly reduced LINC01615 expression in lung cancer cell lines while enhancing apoptosis rates. Therefore, these nanoparticles could be considered a promising therapeutic candidate for treating cancers with overexpression of LINC01615.

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精准纳米医学:以 LINC01615 为靶点的拉帕替尼负载壳聚糖-金纳米粒子用于肺癌治疗
长非编码RNA(lncRNA)通过影响细胞增殖、凋亡和转移途径,作为致癌因子在癌症进展中发挥着至关重要的作用。本研究旨在调查 LINC01615 在流行性癌症中的表达变化,探讨其与患者死亡率的相关性,并介绍一种降低 LINC01615 表达的新型治疗方法。利用癌症基因组图谱(TCGA)数据,分析了LINC01615在各种癌症中的表达变化,并通过Cox回归分析评估了其与患者生存率的关系。通过网络分析确定了与LINC01615相关的共表达通路。利用 GSE38376 研究确定了降低 LINC01615 表达的潜在药物。此外,我们还制作了壳聚糖包裹的纳米颗粒,并用已确定的药物拉帕替尼进行功能化,以检测其对肺癌细胞系的影响以及 LINC01615 表达的变化。我们的研究结果表明,LINC01615在多种常见癌症中表达升高,尤其是在肺癌中,这与肺癌、乳腺癌和肾癌的不良预后有关。共表达网络分析表明,LINC01615 与转移相关基因有关。通过 GEO 数据发现,拉帕替尼能有效调节 LINC01615 的表达。与拉帕替尼共轭的壳聚糖-金纳米粒子能显著降低肺癌细胞系中 LINC01615 的表达,同时提高细胞凋亡率。因此,这些纳米颗粒可被视为治疗LINC01615过表达癌症的一种有前途的候选疗法。
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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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