Protein corona guided albumin-binding paclitaxel nanoparticles for treatment of intracranial tumors

Albumin-bound paclitaxel (Abraxane) exhibits potent antitumor activity, but its suboptimal pharmacokinetics and the restrictive blood-brain barrier (BBB) greatly limit the broader application of albumin-based paclitaxel formulations in intracranial tumors. In this work, we engineered size-uniform (~ 160 nm) paclitaxel-albumin nanoparticles (Fe 3+ @SA-PTX) via simple one-step nano-precipitation method guided by a “protein corona intervention” strategy. During nanoparticle fabrication, tannic acid-Fe 3+ (TA-Fe 3+ ) were strategically introduced. On the one hand, the introduction of TA-Fe 3+ shell could slow down the leakage of paclitaxel and improving the stability and pharmacokinetic profile of the nanoparticles. On the other hand, the presence of Fe 3+ enabled the nanoparticles to interact with unsaturated transferrin in plasma, forming a stable transferrin protein corona. This endowed the nanoparticles with enhanced tumor-targeting capability and the ability to penetrate the BBB. The Fe 3+ @SA-PTX exhibited superior pharmacokinetics and therapeutic efficacy against intracranial tumors via intravenous administration.