Photonic control of ligand nanospacing in self-assembly regulates stem cell fate

Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Covalent organic framework nanomedicines:Biocompatibility for advanced nanocarriers and cancer theranostics applications

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area.The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs,such as poor localization at the tumor site,high drug doses and toxicity,recurrence,and poor immune response.However,inadequate biocompatibility restricts their potential in clinical translation.Therefore,advanced nanomaterials with high biocompat-ibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines.Intrinsic properties of nanoscale covalent organic frameworks(nCOFs),such as suitable size,modular pore geometry and porosity,and straightforward post-synthetic modification via simple organic transformations,make them incredibly attractive for future nanomedicines.The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery.This review summarizes recently published applications of COFs in drug delivery,photo-immuno therapy,sonodynamic therapy,photothermal therapy,chemotherapy,pyroptosis,and combination therapy.Herein we mainly focused on modifications of COFs to enhance their biocompatibility,efficacy and potential clinical translation.This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nano-medicines and will help in the rapid development of cancer drug carriers and theranostics.