Cytomembrane-mimicking nanocarriers with a scaffold consisting of a CD44-targeted endogenous component for effective asparaginase supramolecule delivery.

Highly effective and safe delivery of therapeutic enzymes is pivotal to the success of antitumor therapy. Herein, we report on a targeted enzyme delivery system based on cytomembrane-mimicking nanocarriers (CmN) and a supramolecular technique (SmT). Specifically, each CmN had a scaffold that mainly consisted of a CD44-targeted endogenous component conjugated with polyethylene glycol 2000 (HA-g-PEG) that self-assembled with α-cyclodextrin (ACD). The CmN acted as a microbioreactor with an inner hollow space with the capacity to confine the large molecule asparaginase (Asp) in an Asp/ACD-supramolecular complex conjugated to the inner region. The supramolecular Asp loaded into the CmN (A-S-CmN) exhibited superior stability, kinetic properties, catalytic activity and antitumor effects compared to free Asp due to the dual protection of the supramolecular complex and the nanovesicle, the CD44 targeting-homing ability, the prolonged effects of HA-g-PEG, and the favorable inner microenvironment of the constructed supramolecular CmN. The A-S-CmN also showed a decrease in in vivo toxicity and immunogenicity. CmN combined with SmT therapeutics are easy to implement and extend for use in the delivery of various enzymes and for many types of cancer treatment.