School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China.
Department of Research and Development, Shandong Kanghua Biotechnology Co., Ltd., Weifang, Shandong 261057, P.R. China.
Int J Mol Med. 2024 Aug;54(2). doi: 10.3892/ijmm.2024.5394. Epub 2024 Jul 4.
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 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 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.
在全球范围内,非小细胞肺癌(NSCLC)对人类健康构成重大威胁,占肺癌病例的>80%。顺铂(CDDP)是临床治疗中常用的药物,人们一直致力于通过将其封装在脂质体中来减轻其强烈的毒性,这是研究的重点。然而,出现了一些挑战,例如药物装载效率降低和非特异性释放。本研究旨在通过预先制备 CDDP 并通过将花生凝集素(PNA)作为配体(载有 CDDP 的 PNA 修饰的脂质体(CDDP-PNA-Lip))修饰脂质体表面来提高 CDDP 在脂质体中的包封效率。该策略旨在增强 CDDP 向肿瘤组织的递送,从而减少相关的副作用。通过研究阐明了 CDDP-PNA-Lip 对高表达 MUC1 的 NSCLC 细胞系增殖和迁移的影响。此外,通过异种移植肿瘤实验评估了 PNA 修饰增强脂质体靶向抗癌作用的能力。结果表明,在体外摄取实验中,与游离 RhB 相比,细胞摄取 Rhodamine B(RhB)负载的 PNA 修饰的脂质体的效率提高了约 50%。此外,与游离 CDDP 相比,CDDP-PNA-Lip 使肿瘤抑制作用增强了 2.65 倍。这些发现表明,将 CDDP 封装在配体修饰的脂质体中可能显著提高其肿瘤靶向能力,为临床药物开发提供了有价值的见解。