Biomimetic lipidic nanovectors for effective asparaginase supramolecule delivery

Effectiveness of enzyme therapy is limited by enzyme drawbacks such as short half-life, low bioavailability and high immunogenicity. We loaded asparaginase (Aase) into hydroxypropyl- or sulfonbutylether-beta cyclodextrin to form supramolecular amphiphilic molecules by self-assembly followed by entrapment inside the cores of two biomimetic lipidic nanovectors (AS-XLNs). Supramolecular structure was simulated by molecular docking. AS-XLNs maintained superior activity through isolating Aase from external environment due to docking with cyclodextrin and coating with biomimetic membrane. Fluorescent probes and computational simulations were used to reveal possible interactions between serum albumin/trypsin and Aase/nanovector membrane components which were partly responsible for enhanced bioavailability and bioactivity of AS-XLNs compared to Aase. AS-XLNs significantly increased cytotoxicity against pulmonary tumor cells due to synergistic effects of Aase and nanovector membrane components (killing tumor cells through apoptosis induced by asparagine depletion and autophagy inhibition or via targets such as vascular endothelial growth factor A, alpha-amylase, p-selectin or androgen receptor).