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In Silico Identification and Verification of the Anticancer Mechanism of TMBM-010 from Oxytropis herba with a
Zhe Zhang1, Hui Zheng1, Jindian Fan1
1Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences, Tianjin Medical University, Tianjin 300070, China.
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.
Insights
A novel nanomedicine strategy using TMBM-010-loaded nanoparticles (TNPs@RGD-CM) shows promise for gastric cancer treatment. These nanoparticles enhance drug delivery and efficacy, targeting cancer cells and suppressing tumor growth.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Gastric cancer presents a significant health challenge with limited effective treatments and poor patient prognoses.
- Current therapies for gastric cancer are associated with considerable adverse effects and suboptimal clinical outcomes.
Purpose of the Study:
- To investigate the anticancer potential of the natural compound TMBM-010 using network pharmacology.
- To develop and evaluate TMBM-010-loaded biomimetic nanoparticles (TNPs@RGD-CM) for improved gastric cancer therapy.
Main Methods:
- Network pharmacology was employed to elucidate the anticancer mechanisms of TMBM-010.
- TMBM-010-loaded nanoparticles (TNPs) and gastric cancer cell membrane-coated biomimetic nanoparticles (TNPs@RGD-CM) were synthesized.
- The stability, biosafety, and controlled release of TNPs@RGD-CM were assessed.
- Anticancer efficacy was evaluated in a gastric cancer xenograft mouse model.
Main Results:
- Network pharmacology identified TMBM-010's mechanisms, including ROS induction, DNA damage, apoptosis, and DNA repair inhibition.
- TNPs@RGD-CM exhibited high stability, excellent biosafety, and controlled drug release.
- In vivo studies showed TNPs@RGD-CM significantly enhanced TMBM-010 bioavailability, increased ROS generation, and suppressed tumor growth.
Conclusions:
- TNPs@RGD-CM effectively augment TMBM-010's bioactivity in vivo.
- This nanomedicine strategy demonstrates targeted delivery to cancer cells and suppression of tumor-promoting pathways.
- TNPs@RGD-CM represent a promising novel therapeutic approach for gastric cancer treatment.
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