Dual-Integrin-Targeted Supramolecular Peptide Nanoarchitectonics for Enhanced Hepatic Delivery and Antifibrotic Therapy.

The integration of integrin-binding peptides within self-assembling building blocks is crucial for the development of targeted nanoarchitectonics. However, such constructs typically incorporate only a single integrin-binding peptide, limiting their multifunctionality. Herein, a rationally designed self-assembling peptide with dual integrin-binding motifs for α5β1 and αvβ3 is presented.

Supramolecular Nanoparticles of Histone and Hyaluronic Acid for Co-Delivery of siRNA and Photosensitizer In Vitro.

Small interfering RNA (siRNA) has significant potential as a treatment for cancer by targeting specific genes or molecular pathways involved in cancer development and progression. The addition of siRNA to other therapeutic strategies, like photodynamic therapy (PDT), can enhance the anticancer effects, providing synergistic benefits. Nevertheless, the effective delivery of siRNA into target cells remains an obstacle in cancer therapy.

Supramolecular Nanoarchitectonics Based on Antagonist Peptide Self-Assembly for Treatment of Liver Fibrosis.

Therapeutic peptides have attracted increasing attention as anti-fibrotic drug candidates. However, the rapid degradation and insufficient liver accumulation of therapeutic peptides have seriously hampered their clinical translation. Here, the use of supramolecular nanoarchitectonics is reported to fabricate nanodrugs from therapeutic peptides for treating liver fibrosis.

Peptide-Based Nanoarchitectonics for the Treatment of Liver Fibrosis.

Liver fibrosis is a process of excessive accumulation of extracellular matrix caused by liver injury. Liver fibrosis can progress to cirrhosis or even liver cancer without proper intervention. Until now, no effective therapeutic drugs have been clinically approved for treating liver fibrosis.

Novel active stealth micelles based on βM achieved effective antitumor therapy.

Micelles have been extensively investigated as drug delivery systems for loading of antitumor drugs with the advantages of good dispersibility, controllable size distribution, and high loading capacity. However, phagocytic clearance by the mononuclear phagocyte system remains a major impediment that inhibits blood circulation and thus tumor accumulation of micelles. Inspired by the antiphagocytic properties of β-microglobulin (βM), here we developed a βM-derived peptide for the surface functionalization of micelles.

Amino-Acid-Encoded Supramolecular Photothermal Nanomedicine for Enhanced Cancer Therapy.

Photothermal nanomedicine based on self-assembly of biological components, with excellent biosafety and customized performance, is vital significance for precision cancer therapy. However, the programmable design of photothermal nanomedicine remains extremely challenging due to the vulnerability and variability of noncovalent interactions governing supramolecular self-assembly. Herein, it is reported that amino acid encoding is a facile and potent means to design and construct supramolecular photothermal nanodrugs with controlled therapeutic activities.

Functional Nanomaterials Based on Self-Assembly of Endogenic NIR-Absorbing Pigments for Diagnostic and Therapeutic Applications.

Endogenic pigments derived from hemoglobin have been successfully applied in the clinic for both imaging and therapy based on their inherent photophysical and photochemical properties, including light absorption, fluorescence emission, and producing reactive oxygen species. However, the clinically approved endogenic pigments can be excited only by UV/vis light, restricting the penetration depth of in vivo applications. Recently, endogenic pigments with NIR-absorbing properties have been explored for constructing functional nanomaterials.

Self-assembly of amino acids toward functional biomaterials.

Biomolecules, such as proteins and peptides, can be self-assembled. They are widely distributed, easy to obtain, and biocompatible. However, the self-assembly of proteins and peptides has disadvantages, such as difficulty in obtaining high quantities of materials, high cost, polydispersity, and purification limitations.

Supramolecular Nanodrugs Based on Covalent Assembly of Therapeutic Peptides toward In Vitro Synergistic Anticancer Therapy.

Therapeutic peptides have attracted significant attention in clinical applications due to their advantages in biological origination and good biocompatibility. However, the therapeutic performance of peptides is usually hindered by their short half-lives in blood and inferior activity. Herein, supramolecular nanodrugs of therapeutic peptides are constructed by covalent assembly of chemotherapeutic peptides through genipin cross-linking.

Biomimetic Nanozymes Based on Coassembly of Amino Acid and Hemin for Catalytic Oxidation and Sensing of Biomolecules.

Nanoassemblies based on self-assembly of biological building blocks are promising in mimicking the nanostructures, properties, and functionalities of natural enzymes. However, it remains a challenge to design of biomimetic nanozymes with tunable nanostructures and enhanced catalytic activities starting from simple biomolecules. Herein, the construction of nanoassemblies through coassembly of an amphiphilic amino acid and hemin is reported.

Porphyrin/Ionic-Liquid Co-assembly Polymorphism Controlled by Liquid-Liquid Phase Separation.

Understanding and controlling multicomponent co-assembly is of primary importance in different fields, such as materials fabrication, pharmaceutical polymorphism, and supramolecular polymerization, but these aspects have been a long-standing challenge. Herein, we discover that liquid-liquid phase separation (LLPS) into ion-cluster-rich and ion-cluster-poor liquid phases is the first step prior to co-assembly nucleation based on a model system of water-soluble porphyrin and ionic liquids. The LLPS-formed droplets serve as the nucleation precursors, which determine the resulting structures and properties of co-assemblies.

Self-Assembling Proteins for Design of Anticancer Nanodrugs.

Inspired by the diverse protein-based structures and materials in organisms, proteins have been expected as promising biological components for constructing nanomaterials toward various applications. In numerous studies protein-based nanomaterials have been constructed with the merits of abundant bioactivity and good biocompatibility. However, self-assembly of proteins as a dominant approach in constructing anticancer nanodrugs has not been reviewed.

Supramolecular Nanodrugs Constructed by Self-Assembly of Peptide Nucleic Acid-Photosensitizer Conjugates for Photodynamic Therapy.

Two hybrid materials were designed by conjugating peptide nucleic acids (PNAs) to porphyrin or boron-dipyrromethene, generating PNA-porphyrin (PNA-TPP) and PNA-BODIPY (PNA-BDP) conjugates, respectively. Because of the combination of the supramolecular characteristics of PNAs and photosensitizers, the two hybrid conjugates readily self-assemble in aqueous solutions and produce well-defined nanoparticles with uniform particle sizes. The resulting two kinds of nanoparticles show good stability in biological solutions and upon dilution.

Injectable self-assembled bola-dipeptide hydrogels for sustained photodynamic prodrug delivery and enhanced tumor therapy.

Supramolecular peptide materials have attracted increasing attention due to their natural biological origin and versatile applications. However, it is often challenging to control and modulate the self-assembly of peptides (especially short peptides) for constructing hydrogels with tunable mechanical properties and adaptive injectability toward biomedical applications. Here, we report a supramolecular strategy for forming robust and injectable hydrogels based on the self-assembly of a rationally designed bola-dipeptide.

Self-assembled injectable biomolecular hydrogels towards phototherapy.

Biomolecular hydrogels assembled from biomolecules, such as proteins, peptides, and polysaccharides, are promising candidates for facilitating biomedical applications due to their advantages of high biocompatibility, adjustable mechanical properties, functional diversity, and good degradability. This review focuses on current progress in the field of supramolecular injectable biomolecular hydrogels and their applications in antitumor photodynamic therapy (PDT), photothermal therapy (PTT), combined PDT and PTT, and antibacterial phototherapy with emphasis on biomolecular hydrogelators, injectable behaviors, phototherapeutic functions, and the remaining challenges. We hope that this review can provide useful inspiration for the construction and biological applications of novel photo-functional hydrogels as well as phototherapies.

Supramolecular Protein Nanodrugs with Coordination- and Heating-Enhanced Photothermal Effects for Antitumor Therapy.

Supramolecular protein nanodrugs provide opportunities for improving antitumor therapeutic efficiency and lowering toxicity. However, protein nanodrugs that have robust structural stability and enhanced therapeutic efficiency are still in infancy. In this study, photothermal protein nanodrugs are constructed through a supramolecular approach along with heating by using proteins, photosensitizers, and metal ions as the building blocks.

Robust Photothermal Nanodrugs Based on Covalent Assembly of Nonpigmented Biomolecules for Antitumor Therapy.

Photothermal nanodrugs based on biomolecules are critically important for advancing photothermal therapy (PTT). However, constructing photothermal nanodrugs from biomolecules is highly challenging because most biomolecules are inherently nonpigmented. Herein, we synthesize well-defined, uniform photothermal nanodrugs through a covalent assembly approach by using nonpigmented peptides and iridoids as building blocks.

Nucleation and Growth of Amino Acid and Peptide Supramolecular Polymers through Liquid-Liquid Phase Separation.

The transition of peptides and proteins from the solution phase into fibrillar structures is a general phenomenon encountered in functional and aberrant biology and is increasingly exploited in soft materials science. However, the fundamental molecular events underpinning the early stages of their assembly and subsequent growth have remained challenging to elucidate. Here, we show that liquid-liquid phase separation into solute-rich and solute-poor phases is a fundamental step leading to the nucleation of supramolecular nanofibrils from molecular building blocks, including peptides and even amphiphilic amino acids.

High-tolerance crystalline hydrogels formed from self-assembling cyclic dipeptide.

Peptide-based supramolecular hydrogels, as a new type of biological nanoarchitectonic structure, hold great promise for a wide range of biomedical and nanotechnological applications, such as tissue engineering, drug delivery, and electronic and photonic energy storage. In this work, a cyclic dipeptide (CDP) cyclo-(Trp-Tyr) (C-WY), which has exceptional structural rigidity and high stability, is selected as a hydrogelator for the formation of supramolecular hydrogels. The unique hydrogen bonding in C-WY endows a high propensity for self-assembly and the resulting hydrogels are revealed to be crystalline.

Peptide-modulated self-assembly as a versatile strategy for tumor supramolecular nanotheranostics.

Advances in supramolecular self-assembly have promoted the development of theranostics, the combination of both therapeutic and diagnostic functions in a single nanoplatform, which is closely associated with antitumor applications and has shown promising potential in personalized medicine. Peptide-modulated self-assembly serves as a versatile strategy for tumor supramolecular nanotheranostics possessing controllability, programmability, functionality and biosafety, thus promoting the translation of nanotheranostics from bench to bedside. In this review, we will focus on the self-assembly of peptide-photosensitizers and peptide-drugs as well as multicomponent cooperative self-assembly for the fabrication of nanotheranostics that integrate diagnosis and therapeutics for antitumor applications.

Photoactive properties of supramolecular assembled short peptides.

Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short peptides are among the most preferred building blocks as they can self-assemble to form versatile supramolecular architectures displaying unique physical and chemical properties, including intriguing optical features. Herein, we discuss the progress made over the past few decades in the design and characterization of optical short peptide nanomaterials, focusing on their intrinsic photoluminescent and waveguiding performances, along with the diverse modulation strategies.

Self-Assembling Endogenous Biliverdin as a Versatile Near-Infrared Photothermal Nanoagent for Cancer Theranostics.

Photothermal nanomaterials that integrate multimodal imaging and therapeutic functions provide promising opportunities for noninvasive and targeted diagnosis and treatment in precision medicine. However, the clinical translation of existing photothermal nanoagents is severely hindered by their unclear physiological metabolism, which makes them a strong concern for biosafety. Here, the utilization of biliverdin (BV), an endogenic near-infrared (NIR)-absorbing pigment with well-studied metabolic pathways, to develop photothermal nanoagents with the aim of providing efficient and metabolizable candidates for tumor diagnosis and therapy, is demonstrated.

The Dominant Role of Oxygen in Modulating the Chemical Evolution Pathways of Tyrosine in Peptides: Dityrosine or Melanin.

In diverse biological systems, the oxidation of tyrosine to melanin or dityrosine is crucial for the formation of crosslinked proteins and thus for the realization of their structural, biological, and photoactive functionalities; however, the predominant factor in determining the pathways of this chemical evolution has not been revealed. Herein, we demonstrate for tyrosine-containing amino acid derivatives, peptides, and proteins that the selective oxidation of tyrosine to produce melanin or dityrosine can be readily realized by manipulating the oxygen concentration in the reaction system. This oxygen-dependent pathway selection reflects the selective chemical evolution of tyrosine to dityrosine and melanin in anaerobic and aerobic microorganisms, respectively.

Coordination-assembled supramolecular nanoplatforms: structural modulation and theranostic applications.

Theranostics possessing great potential in the treatment of various diseases gain attentions in recent years. Coordination-assembled supramolecular nanoplatforms are emerged as promising candidates for theranostic applications. With the facile, robust and versatile fabrication, these systems overcome the drawbacks of many existing theranostic nanoplatforms.

An injectable dipeptide-fullerene supramolecular hydrogel for photodynamic antibacterial therapy.

Photodynamic therapy (PDT) is a promising treatment against multiantibiotic-resistant bacteria with the advantage of a low tendency towards antibiotic resistance. Due to their high PDT efficiencies and superior chemical stabilities, fullerenes have been proposed as effective photosensitizers for the photodynamic inactivation of bacteria. However, the biomedical applications of fullerenes are hindered by their limited aqueous solubility and apparent tendency to undergo aggregation.