In Silico Identification and Verification of the Anticancer Mechanism of TMBM-010 from Oxytropis herba with a Rational Delivery System Design.

Abstract

Patients diagnosed with gastric cancer often face poor prognoses and limited treatment options. Current therapies remain limited, resulting in significant adverse effects and suboptimal outcomes. Network pharmacology analysis suggests that TMBM-010, a natural compound, holds the potential to modulate key pathways in cancer progression. Through network pharmacological analysis, we identified the anticancer mechanisms of TMBM-010, including ROS induction, DNA damage, apoptosis, and inhibition of DNA repair pathways. To enhance the bioavailability and efficacy of TMBM-010, we developed TMBM-010-loaded nanoparticles (TNPs) and biomimetic nanoparticles (TNPs@RGD-CM) coated with gastric cancer cell membranes and RGD ligands. TNPs@RGD-CM demonstrated high stability, excellent biosafety, and a controlled release profile. In a gastric cancer xenograft model, TNPs@RGD-CM significantly improved the bioavailability, increased ROS generation, and enhanced anticancer effects. Our findings demonstrate that TNPs@RGD-CM augment TMBM-010's bioactivity in vivo, effectively targeting cancer cells and suppressing tumor-promoting pathways. These results suggest that TNPs@RGD-CM represent a promising nanomedicine strategy for gastric cancer treatment.