Journal Article

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

Wu, Yuanlin, Zhang, Jiandong, Zhao, Junjun, Wang, Bin

2024

Overview

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 internalization 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Apoptosis / Cancer / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Cell Line, Tumor / Cell migration / Cell Proliferation / Chemotherapy / Cisplatin / Cisplatin - pharmacology / Cisplatin - therapeutic use / Critical Care Medicine / DDP-resistance / Dialysate / Dosage and administration / Drug delivery systems / Drug resistance / Drug Resistance, Neoplasm / Drug therapy / Drugs / Efficiency / Flow cytometry / Folic acid / Fourier transforms / Humans / Immunofluorescence / Intensive / Internal Medicine / Internalization / Liposomes / Liposomes - therapeutic use / Lung cancer / Lung cancer, Non-small cell / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Medicine / Medicine & Public Health / Methods / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miR-219a-5p / Nano-drug delivery system / Nanomaterials / Nanoparticles / Non-small cell lung carcinoma / NSCLC / Nuclease / Patient outcomes / Pneumology/Respiratory System / Small cell lung carcinoma / Toxicity / Tumor cells / Vehicles