Nanoparticle Albumin-Bound Bortezomib: Enhanced Antitumor Efficacy and Tumor Accumulation in Breast Cancer Therapy.

Nanoparticle albumin-bound (NAB) formulations are emerging as a viable strategy for the intravenous delivery of poorly water-soluble drugs. This study aims to improve the therapeutic profile of Bortezomib (BTZ), addressing its low solubility and significant systemic toxicity through the development of NAB-BTZ nanoparticles. The synthesized nanoparticles exhibited an average size of 296.47 ± 10 nm and a high drug encapsulation efficiency of 75%, and a drug loading of 10%. NAB-BTZ displayed a controlled, pH-sensitive release profile, with 59% release at pH 5.4 (mimicking tumor environments) and 46% at pH 7.4 after 12 h. In vitro assays demonstrated that NAB-BTZ significantly reduced the viability of 4T1 mammary carcinoma cells in a dose- and time-dependent manner, increasing late apoptosis from 6% to 54% after 48 h, compared to 24% for free BTZ. At molecular level, NAB-BTZ induced apoptosis by upregulating p53 and Bax, downregulating Bcl-2, and activating caspases 3 and 7. In vivo tests in a murine 4T1 breast cancer model showed that NAB-BTZ substantially inhibited tumor growth, achieving an average tumor volume of 916 mm³ by day 31 versus 1400 mm³ for free BTZ, leading to an improved survival rate of 100% compared to 83% in the BTZ group. Technetium-99m (^99mTc) labeling and SPECT imaging confirmed enhanced targeting capability, showing preferential accumulation of NAB-BTZ in tumor sites compared to free BTZ. These findings suggest that NAB-BTZ not only improves antitumor efficacy but also enhances its safety profile, underscoring its clinical potential in breast cancer therapy.