Folate‐Targeted Liposomal Co‐Delivery of Methotrexate and Antisense HULC for Colorectal Cancer: In Vitro Therapeutic Evaluation

Abstract

Colorectal cancer is mentioned as the third most common type of diagnosed malignancy worldwide. Therefore, a novel folic acid (FA)‐functionalized liposomal nanocarriers containing methotrexate (MTX) and antisense lncRNA HULC were developed against HCT116 colorectal cancer cells. The fabricated nanocarrier (LDT‐A) was characterized by FT‐IR, DLS, AFM, and TEM devices. The hydrodynamic diameter of 102 nm and surface charge of +31 mV were measured for the LDT‐A nanocarrier. The TEM indicated a size range of 100 to 150 nm, and AFM analysis confirmed the uniformity and spherical morphology of the LDT‐A nanocarrier. The controlled (5% after 4 h of incubation at pH 7.4) and pH‐sensitive (50% within 4 h of incubation at pH 5.0) release rate of antisense lncRNA HULC was observed. MTT assay demonstrated 14% cell viability after 72 h of treatment with 20 µg/mL of LDT‐A. The IC 50 concentration of the nanocarrier resulted in a two to threefold reduction in the expression of IGF2BP1, SPHK1, and SLC35A3 genes involved in tumor progression. The expression of BAX (apoptosis) and mTORC1 (autophagy‐related signaling) genes was enhanced by 3 and above 11 folds after treatment with nanocarrier while BCL2 (antiapoptotic) and ATG5 (autophagy) genes showed no significant change. 10. 8% apoptosis and 11.59% cell cycle arrest were observed in cancer cells after treatment with IC 50 concentration of LDT‐A while ROS assessment exhibited 62.5% viable cells. About 99% cellular uptake was detected for FA‐decorated LDT‐A. These data support the potential capability of LDT‐A in the suppression of colorectal cancer.