用花生凝集素修饰的脂质体提高顺铂在非小细胞肺癌中的给药疗效

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2024-08-01 Epub Date: 2024-07-04 DOI:10.3892/ijmm.2024.5394
Ben Yang, Rongguan Kou, Hui Wang, Anping Wang, Lili Wang, Sipeng Sun, Mengqi Shi, Shouzhen Zhao, Yubing Wang, Yi Wang, Jingliang Wu, Fei Wu, Fan Yang, Meihua Qu, Wenjing Yu, Zhiqin Gao
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引用次数: 0

摘要

在全球范围内,非小细胞肺癌(NSCLC)是人类健康的重大威胁,占肺癌病例的 80% 以上。顺铂(CDDP)是临床治疗中的常用药物,一直是研究的重点,目的是通过脂质体包封减轻其剧毒性。然而,药物负载效率降低和非特异性释放等挑战已成为障碍。本研究旨在通过预先制备 CDDP,并通过加入花生凝集素(PNA)作为配体来修饰脂质体表面[CDDP-负载 PNA 修饰脂质体(CDDP-PNA-Lip)],从而提高 CDDP 在脂质体中的包封效率。这一策略旨在加强 CDDP 向肿瘤组织的输送,从而减少相关的副作用。体外研究阐明了 CDDP-PNA-Lip 对 MUC1 高表达的 NSCLC 细胞株的增殖和迁移的影响。此外,还通过异种移植肿瘤实验评估了 PNA 修饰增强脂质体靶向抗肿瘤功效的能力。结果表明,在体外摄取实验中,与游离 RhB 相比,负载 PNA 修饰的罗丹明 B(RhB)脂质体被细胞摄取的效率要高出约 50%。此外,与游离 CDDP 相比,CDDP-PNA-Lip 在体内抑制肿瘤的效果提高了 2.65 倍。这些研究结果表明,将 CDDP 包封在配体修饰的脂质体中可显著提高其肿瘤靶向能力,为临床药物开发提供了宝贵的启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Improved efficacy of cisplatin delivery by peanut agglutinin‑modified liposomes in non‑small cell lung cancer.

Globally, non‑small cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by pre‑preparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDP‑loaded PNA‑modified liposomes (CDDP‑PNA‑Lip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDP‑PNA‑Lip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted anti‑tumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)‑loaded PNA‑modified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDP‑PNA‑Lip resulted in a 2.65‑fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligand‑modified liposomes may significantly improve its tumour‑targeting capabilities, providing valuable insights for clinical drug development.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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