Aptamer-functionalized luteolin-loaded albumin nanoplatform for targeted therapy of HER2-positive breast cancer

A novel anti-solvent ultrasonication method to fabricate luteolin-loaded BSA NPs. • Noncovalent hydrophobic interactions to fabricate aptamer-functionalized Lut-BSA NPs. • Multifunctional nanoplatform integrates natural compounds with nano and aptamer. • Superior tumor inhibition and biosafety highlight clinical translational potential. Luteolin (Lut) is a promising active component derived from traditional Chinese medicine for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, its clinical translation is substantially hindered by intrinsic physicochemical limitations: poor aqueous solubility and lack of tumor-selective biodistribution. So, we fabricated luteolin-loaded bovine serum albumin (BSA) nanoparticles (Lut-BSA NPs) via a modified anti-solvent ultrasonication method, in which BSA functions simultaneously as a biocompatible drug carrier and stabilizing agent. Then, HApt, the HER2-targeted aptamer, was conjugated to the surface of Lut-BSA NPs to generate the targeted nanoplatform HApt-Lut-BSA NPs, which act as a HER2 navigator to enable precise tumor targeting. HApt-Lut-BSA NPs demonstrated a high encapsulation efficiency of 87.64 ± 1.02% and a loading content of 3.87 ± 0.03%. In vitro release studies indicated that HApt-Lut-BSA NPs exhibited favorable release under acidic conditions, facilitating Lut accumulation in tumors. Cellular uptake assays and MTT analysis demonstrated that HApt-Lut-BSA NPs exhibited excellent targeting and cytotoxicity in vitro . In vivo fluorescence imaging confirmed superior accumulation of HApt-Lut-BSA NPs in SK-BR-3 tumor-bearing NPSG mice, while pharmacodynamic evaluation showed pronounced tumor growth inhibition and satisfactory in vivo safety. Collectively, this multifunctional nanoplatform that uniquely integrates a natural compound with nanotechnology and aptamer technology, not only markedly improves druggability and tumor-targeted delivery efficiency, but also offers a broadly applicable paradigm for the delivery of poorly water-soluble therapeutics and may promote the development of clinically translatable targeted drugs. Download: Download high-res image (228KB) Download: Download full-size image