A Biohybrid Lurker-to-Attacker Strategy To Solve Inherent Dilemma of Positively Charged Delivery Nanoparticles

Nonspecific cell attack and rapid in-vivo recognition/clearance have been the unsurmountable hurdles against the application of positively charged nanoparticles (pcNPs). The frequently used active targeting approach by grafting specific ligands onto pcNPs suffers from their strong electrostatic interaction with normal cells. We herein put forward a biohybrid strategy to solve this long-standing dilemma in the development of tumor-specific pcNPs. pcNPs are arranged to put on a biological "coat" derived from cancer cell membranes. This design renders pcNPs the high recognition to the homotypic cancer cells with even higher uptake efficiency than the parent pcNPs, while considerably inhibiting the adsorption by biological components, the macrophage capture, and the uptake by the heterotypic cells (e.g., normal and macrophage cells). Encouragingly, the tumor self-targeting by coating pcNPs with the cancer cell membranes proved to be achievable, allowing the role transition to an "attacker" upon reaching the homologous tumor developed from the source cancer cells. This approach paves a facile way to overcome the current limitations for in vivo application of pcNPs.