A Modularly Designable Vesicle for Sequentially Multiple Loading.

The vesicle is one of the most intriguing platforms for drug delivery, which is believed to improve drug efficacy. In the past few decades, a great deal of materials have been explored to make vesicles, including lipids, block copolymers, dendrons, erythrocyte membranes, and even DNA. Other than shape and size control, most efforts are focused on achieving certain functions, for example, an abundance of stimuli-responsive features are introduced to vesicles, which can be applied to controllable release, such as pH, redox, light, radiation, enzyme etc. Besides, crosslinking or pegylation is used to increase vesicles' stability and elongate circulation time. By incorporating affinity ligands, vesicles can further accumulate to diseased cells or tissues to achieve targeting properties. Recently, multidrug delivery is believed to show a synergy effect in cancer therapy and has become a new direction in this field. However, coloading hydrophilic-hydrophobic small molecules, oligonucleotides, and peptides in the same size- and shape-controlled vesicle through a stepwise manner with high efficiency is still challenging. Herein, a modularly designable vesicle is reported for sequential multiple loading based on frame-guided assembly, which is believed to be an outstanding platform for drug delivery in the future.