Controllable Self‐Assembly of Peptide‐Cyanine Conjugates In Vivo as Fine‐Tunable Theranostics

Abstract

The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging.Here,modularly designed peptide-cyanine conjugates that intracellularly selfassembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties.T he peptide backbone is cleaved by caspase-3/7 after entering the cells.T hen the selfassembled residue,w ith ad ouble cyanine substitution (Pr-2Cy), forms aPhelical column in which H-aggregated cyanine dyes show 3.4-fold photothermal conversion efficiency compared to free ones.T he self-assembled residue with as ingle cyanine substitution (Pr-1Cy)forms aloose column, in which cyanine dyes with undefined structure have af luorescence quantum yield of up to 9.5 %(emission at 819 nm in H 2 O). This work provides as imple wayt om odify in vivo selfassembled peptides with functional molecules for achieving desired bio-applications.

Advances and Perspectives of Peptide and Polypeptide‐Based Materials for Biomedical Imaging

“…More recently, Wang et al also reported a new molecular peptide-cyanine platform with tunable theranostics. [88] This peptide-cyanine platform was modularly designed with a recognition moiety (AVPIAQK) for X-linked inhibitor of apoptosis protein, a responsive moiety (DEVD) for cleavage by caspase-3/7, and a self-assembly moiety (KLVFFAECG or GCKLVFFAECG) for in situ self-assembly. Especially, after responsive moiety was cleaved, self-assembly moiety with two cyanine substitutions could yield enhanced photothermal conversion efficiency while exhibiting high fluorescence quantum yields for one cyanine substitution, due to different aggregation patterns of cyanine.…”

Highly Inoxidizable Heptamethine Cyanine–Glucose Oxidase Conjugate Nanoagent for Combination of Enhanced Photothermal Therapy and Tumor Starvation

“…[ 18 ] ii) The supramolecular strategy of heptamethine cyanine self‐assembly to enhance the intermolecular interactions. [ 19 ] iii) The stable spatial structure frame (e.g., silica nanoparticles, [ 20 ] rotaxane, [ 21 ] and cucurbituril [ 22 ] ) to protect the structure of Cy7. However, in the presence of oxygen, these strategies essentially cannot completely avoid the oxidative decomposition of cyanine dyes.…”

Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy

“…Stimulus-induced self-assembly, which enables molecules to assemble locally at the disease site of interest, has been demonstrated to be an efficient way to realize the purpose of imaging signal amplification, , enhanced therapeutic effects, and improved biosafety. , For example, the enzyme-induced self-assembled supramolecular hydrogels developed by Xu and coworkers have proven the capability to enhance the accumulation and retention time of small-molecule peptides for improved cancer imaging and treatment. − Alternatively, Rao and Liang groups innovatively proposed a concept of an enzyme/GSH-mediated self-assembly approach based on a biorthogonal CBT-Cys condensation reaction, which has been successfully and widely applied for bioimaging applications. − Recently, Wang and coworkers reported a peptide-assembled nanosystem with the assembly-induced retention (AIR) effect to improve the tumor accumulation and antitumor efficacy in vivo. − Nevertheless, the metabolism and the ultimate therapeutic effect of the nanoassembly in living organisms greatly depend on the physical and chemical properties of materials, − especially the particle morphology, , which is one of the most critical factors for boosting the effects of the cellular uptake rate, tumor accumulation, and tissue penetration depth. Stimulus-driven molecular morphology/size transformation has recently been proven to be a powerful tool for constructing intelligent and transformable biomaterials. ,− Upon responding to a variety of stimuli, such as enzymes, − acidic pH, − reductive glutathione (GSH), reactive oxygen species (ROS), − and light, , the biomolecules undergo chemical or structural changes along with size reduction, resulting in deep tumor penetration and new biological effects.…”