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

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.

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.

PTX-loaded microbubbles were synthesized and characterized using dynamic light scattering (particle size, zeta potential), scanning electron microscopy (morphology), and UV spectrophotometry (drug loading efficiency). In vitro 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.

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.

This study demonstrates a nanobiotechnology-based strategy in which ultrasound-triggered PLGA microbubbles serve as an effective carrier for PTX delivery. The findings highlight UTMD as a promising targeted drug delivery platform in medical biotechnology, warranting further in vivo validation for clinical translation in TNBC therapy.