Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer

Sep 22, 2026

Cisplatin resistance often undermines first-line chemotherapy in non-small cell lung cancer (NSCLC), and microRNA-219a-5p is reported to increase DDP sensitivity, yet free miR-219a-5p is unstable due to nuclease degradation in blood. This study constructs a folate-modified liposome nanodrug to deliver cisplatin and miR-219a-5p together with targeted uptake. Characterization shows uniform ~135.8 nm particles, serum-stable miR-219a-5p protection, receptor-mediated binding to A549 cells, improved internalization, and enhanced anti-NSCLC activity with low in vitro toxicity.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Introduction

Wu et al. BMC Pulmonary Medicine (2024) 24:159 [https://doi.org/10.1186/s12890-024-02938-6](https://doi.org/10.1186/s12890-024-02938-6) BMC Pulmonary Medicine RESEARCH Open Access Folate-modified liposomes mediate the co- delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer Yuanlin Wu 1, Jiandong Zhang 1, Junjun Zhao 1 and Bin Wang 1* Abstract Cisplatin (DDP) resistance, often leading to first-line chemotherapy failure in non-small cell lung cancer (NSCLC), poses a significant challenge. MiR-219a-5p has been reported to enhance the sensitivity of human NSCLC to DDP. However, free miR-219a-5p is prone to degradation by nucleases in the bloodstream, rendering it unstable. In light of this, our study developed an efficient nanodrug delivery system that achieved targeted delivery of DDP and miR-219a-5p by modifying liposomes with folate (FA) . Based on the results of material characterization, we successfully constructed a well-dispersed and uniformly sized (approximately 135.8 nm) Lipo@DDP@miR-219a- 5p@FA nanodrug. Agarose gel electrophoresis experiments demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited good stability in serum, effectively protecting miR-219a-5p from degradation. Immunofluorescence and flow cytometry experiments revealed that, due to FA modification, Lipo@DDP@miR-219a-5p@FA could specifically bind to FA receptors on the surface of tumor cells (A549), thus enhancing drug internal ization efficiency. Safety evaluations conducted in vitro demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited no significant toxicity to non-cancer cells (BEAS-2B) and displayed excellent blood compatibility. Cellular functional experiments, apoptosis assays, and western blot demonstrated that Lipo@DDP@miR-219a-5p@FA effectively reversed DDP resistance in A549 cells, inhibited cell proliferation and migration, and further promoted apoptosis. In summary, the Lipo@ DDP@miR-219a-5p@FA nanodrug, through specific targeting of cancer cells and reducing their resistance to DDP, significantly enhanced the anti-NSCLC effects of DDP in vitro, providing a promising therapeutic option for the clinical treatment of NSCLC. Keywords DDP-resistance, FA, miR-219a-5p, NSCLC, Nano-drug delivery system *Correspondence: Bin Wang [wangbinbbin@163.com](wangbinbbin@163.com) 1Department of Thoracic Surgery, Shaoxing People’s Hospital, No.568 Zhongxing North Road, 312000 Shaoxing, Zhejiang, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wu et al. BMC Pulmonary Medicine (2024) 24:159 Introduction Lung cancer is the second most common cancer worldwide, accounting for 11.4% of all cancer cases, and is a primary contributor to cancer-related deaths [1–3]. Non-small cell lung cancer (NSCLC) comprises a large proportion (85%) of all lung cancer patients and is a serious threat to human lif

FAQs

Why is cisplatin resistance a problem in NSCLC?

Cisplatin resistance reduces tumor cell sensitivity to chemotherapy, leading to first-line treatment failure in non-small cell lung cancer.

What issue limits the clinical use of free miR-219a-5p?

Free miR-219a-5p is prone to degradation by nucleases in the bloodstream, making it unstable and lowering delivery effectiveness.

How does folate modification improve the nanodrug’s targeting?

Folate-modified liposomes can bind to folate receptors on the surface of tumor cells (A549), which increases cellular uptake and internalization efficiency.

Sep 22, 2026

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