(E)-Labda dial-Loaded Nanoparticles for Triple Negative Breast Cancer

Introduction: Triple-negative breast cancer (TNBC) is the most aggressive kind of breast cancer, with no hormone receptors and resistance to targeted therapy. Chemotherapy is the current standard; however, it is limited by toxicity, poor response, and high recurrence, emphasising the need for innovative methods. Methods: This study investigates the therapeutic potential of (E)-labda-8(17), 12-diene-15,16-dial ((E)-labda dial), a bioactive chemical found in Curcuma amada (mango ginger) that was formulated into nanoparticles to increase transport and effectiveness. Whole-genome sequencing of TNBC cell lines was used to detect protein-altering mutations, which were then assessed using molecular docking and dynamics simulations to assess (E)-labda dial interactions with key mutant proteins (BRCA1, BRCA2, BARD1, PALB2, TP53, CHEK2). Lipid-based nanoparticles (LNPs) and polymeric nanoparticles (PNPs) were developed and tested for drug encapsulation, release kinetics, and stability. MTT and other functional tests were used to assess cytotoxic effects, and in silico pharmacokinetic models were carried out to anticipate treatment results. Results: Results showed that PNPs outperformed LNPs in terms of encapsulation efficiency, sustained drug release, and tumour inhibition. Docking investigations demonstrated that mutant CHEK2, BARD1, and PALB2 bind to (E)-labda dial more strongly, indicating that carcinogenic pathways may be disrupted. Discussion: These data, taken together, emphasise the abilities of (E)-labda dial-loaded nanoparticles as a targeted treatment method for TNBC, with potential effectiveness and toxicity benefits over traditional chemotherapy. Conclusion: This work lays the basis for precision and personalised treatment for TNBC patients. However, future optimisation and clinical validation of these nanoparticles can be done in future to determine their translational potential for use in practice.