Nanobowl-supported liposomes enhance paclitaxel delivery by improving loading stability and modulating protein corona effect

Liposomes are among the most potent drug delivery nanocarriers in clinical translation, yet the encapsulation of hydrophobic agents within the phospholipid bilayer often possesses limited stability, resulting in accelerated drug leakage and compromised therapeutic efficacy. Here, we report that nanobowl-supported liposomes (NbLipo) can overcome limitations associated with bilayer-loaded drug delivery. The nanobowl embedded within the aqueous cavity of NbLipo resulted in improved encapsulation and loading stability of paclitaxel (PTX), a model hydrophobic drug, with concomitant decreased phospholipid bilayer fluidity and enhanced membrane stability. Proteomic analysis further revealed that nanobowl-supported bilayers reduced serum protein adsorption and modulated the components of the protein corona, characterized by enrichment of CD55 (a complement inhibitor) and downregulation of complements C3 and C5. These effects decreased serum protein-induced drug leakage and complement-mediated blood clearance, leading to superior antitumor efficacy in cytotoxicity and orthotopic 4T1 tumor bearing mice compared with conventional liposomes. This work shows that nanobowl-supported bilayer approaches can improve membrane stability and expand therapeutic potential of liposomal formulations for hydrophobic drugs.