Ultrasound-Triggered Paclitaxel-Loaded PLGA Microbubbles as a Nanobiotechnology Platform for Targeted Therapy of Triple-Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, with limited therapeutic options due to the lack of specific molecular targets and frequent drug resistance. Biotechnological advances in nanocarrier systems and ultrasound-targeted drug delivery provide new opportunities for precision cancer therapy. Objectives: This study aimed to develop paclitaxel (PTX)-loaded poly (lactide-co-glycolide) (PLGA) lipid microbubbles and evaluate whether ultrasound-targeted microbubble destruction (UTMD) could enhance the therapeutic efficacy against TNBC cells. Materials and Methods: anticancer efficacy was assessed through MTT and Transwell assays (cell proliferation and migration), flow cytometry and Western blotting (apoptosis), and mitochondrial damage was analyzed using membrane potential assays and transmission electron microscopy. Results: The PTX-loaded PLGA microbubbles were spherical, well-dispersed, and stable, with an average diameter of 390.5 nm, zeta potential of -22.97 mV, and a drug loading efficiency of 4.34±0.08%. Ultrasound exposure significantly enhanced the inhibitory effects of PTX-loaded microbubbles on TNBC cell proliferation and invasion, promoted apoptosis through Bax/Caspase-3 activation and Bcl-2 downregulation, and exacerbated mitochondrial damage compared with microbubbles or PTX alone. Conclusion: validation for clinical translation in TNBC therapy.