Fabrication of Doxorubicin Nanoparticles Mediated by Folic Acid and Its Effect on the Wnt/β-Catenin Signaling to Improve Precancerous Lesions in Gastric Cancer

Abstract

Doxorubicin hydrochloride (DOX) is an anthracycline broad-spectrum antitumor drug, but it can produce a wide range of cytotoxicities in the body. Intravenous injection of a high dose of DOX causes serious toxicity and side effects in the heart and spinal cord. These shortcomings limit the clinical adoption of DOX. In this work, folic acid was coupled to DOX albumin nanoparticles (NPs) by chemical modification so that the preparation could actively target tumor site accumulation and release DOX to inhibit tumor cells. Albumin NPs were prepared by the desolvation method, and the formulation and preparation process were optimized. The particle size and granularity were taken as evaluation indexes. The in vitro antitumor activity of folic acid-mediated DOX albumin NPs against human hepatoma cell HepG2 and human gastric cancer cell SGC7901 was evaluated by using the methyl tetrazolium (MTT) assay with commercial DOX as a reference. Twenty SD rats were utilized to participate in the efficacy analysis of folic acid-mediated DOX albumin NPs for gastric precancerous lesions (GPLs). The results showed that the average particle size of folate-mediated doxorubicin albumin NPs was 267.28±0.38 nm, and 90% of them were less than 280.00 nm, showing a uniform particle size distribution. The drug release rate of the NPs within 24 h was 27.3%, and the NPs had sustained release properties. The IC50 values of the NPs and DOX aqueous solution on the highly expressed HepG2 cells were 4.78 μmol/L and 5.26 μmol/L, respectively, and those on the SGC7901 cells were 4.62 μmol/L and 5.06 μmol/L, respectively. After the establishment of the GPL model, the gene levels in the Wnt/β-catenin signaling were markedly upregulated (P <0.05). Folic acid-mediated doxorubicin albumin NPs greatly inhibited the abnormal expression of the above genes (P <0.01), i.e., they could effectively prevent further precancerous lesions of gastric cancer.