Virus-Inspired Mimics Based on Dendritic Lipopeptides for Efficient Tumor-Specific Infection and Systemic Drug Delivery

Herein, multifunctional mimics of viral architectures and infections self-assembled from tailor-made dendritic lipopeptides for programmed targeted drug delivery are reported. These viral mimics not only have virus-like components and nanostructures, but also possess virus-like infections to solid tumor and tumor cells. Encouragingly, the viral mimics provide the following distinguished features for tumor-specific systemic delivery: i) stealthy surface to resist protein interactions and prolong circulation time in blood, ii) well-defined nanostructure for passive targeting to solid tumor site, iii) charge-tunable shielding for tumor extracellular pH targeting, iv) receptor-mediated targeting to enhance tumor-specific uptake, and v) supramolecular lysine-rich architectures mimicking viral subcellular targeting for efficient endosomal escape and nuclear delivery. This bioinspired design make in vivo tumor suppression by drug-loaded viral mimics against BALB/c mice bearing 4T1 tumor greatly exceed the positive control group (more than three times). More importantly, viral mimics hold great potentials to reduce side effects and decrease tumor metastasis after systemic administration.