Optimizing in vitro lung cancer therapy with folate-conjugated polydopamine-coated liposomes loaded with gemcitabine

Surface-altered, targeted nanocarriers play crucial roles in chemotherapy. Incorporating ligands into polymers may alter their chemical composition, potentially compromising their drug storage and encapsulation capacity. Polydopamine (PDA) is a novel, biocompatible, and versatile agent for producing targeted nanoparticles that serve as a base for conjugating specific ligands to non-reactive polymeric nanocarriers. This investigation aimed to evaluate whether gemcitabine (GEM)-loaded liposomes conjugated with PDA could enhance cancer treatment.

A series of liposomes, named plain GEM, GEM@FA, and GEM@FA/PDA, was designed. Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS) were used to confirm the presence of PDA coating and folic acid (FA) and PDA conjugations. Cellular uptake, cytotoxicity, and cell death were evaluated using biochemical and flow cytometric assays.

Compared to typical liposomes, GEM@FA/PDA liposomes were smaller, more stable, and exhibited a spherical shape with excellent cellular uptake. GEM@FA and GEM@FA/PDA liposomes showed significantly higher cytotoxicity against lung cancer (H1299) cells compared to GEM liposomes and pure GEM solution at all concentrations, while causing much less cytotoxicity to normal cells (NIH3T3).

GEM@FA/PDA liposomes demonstrated enhanced cancer-fighting effectiveness while minimizing harm to healthy tissues, making them a promising approach for chemotherapy.