A Modularly Designable Vesicle for Sequentially Multiple Loading

Abstract

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.

Cellular Ingestible DNA Nanostructures for Biomedical Applications

“…Liu et al employed the frame‐guided assembly (FGA) strategy to develop a modularly designable vesicle for sequential multiple loading (Figure 3E). [ 64 ] With this vesicle, they accomplished programmatically loading of four different functional substances through layer‐by‐layer assembly. The FGA strategy provided a potential approach for the delivery of multiple functional groups and realized the combination of therapeutic function and tracking purpose.…”

Frame-Guided Assembly of Amphiphiles

“…On the basis of the good biocompatibility of PPO and DNA molecules, PPO systems also demonstrated the capability to construct modular vesicles for sequential multiple loadings of small hydrophilic/hydrophobic molecules and oligonucleotides (Figure 8a). 46 Furthermore, good enzyme resistance was also observed due to the existence of the inner-frame, wherein the interior DNA could be kept intact for more than 1 week while incubated with the DNA enzyme, providing a potential platform for drug delivery. 47 To break the vesicles and realize controllable drug release, disulfide bonds were introduced into the frame, which could be cleaved to deform the assembly, resulting in the release of the loaded molecules under physiological conditions (Figure 8b).…”

“…On the basis of the good biocompatibility of PPO and DNA molecules, PPO systems also demonstrated the capability to construct modular vesicles for sequential multiple loadings of small hydrophilic/hydrophobic molecules and oligonucleotides (Figure a) . Furthermore, good enzyme resistance was also observed due to the existence of the inner-frame, wherein the interior DNA could be kept intact for more than 1 week while incubated with the DNA enzyme, providing a potential platform for drug delivery .…”

“…(a) Sequential multiple loadings of small hydrophilic/hydrophobic molecules and oligonucleotides into assemblies. Reproduced with permission from ref . Copyright 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany.…”

Controlling the two components modified on nanoparticles to construct nanomaterials

“…In addition, it can be extended to a variety of colloidal material combinations according to the change of the size and proportion of nanoparticles, which may be of great help in the construction of complex systems of temperature responsive multifunctional materials. In particular, Liu and coworkers 15,17,41,42 have done a lot of work in this field. They reported the frame-guided self-assembly strategy by modifying oligonucleotide chains or copolymers containing DNA chains on gold nanoparticles, such as poly(propylene oxide) (PPO)-b-DNA.…”