Self-Assembly of an Antitumor Dipeptide Induced Near-Infrared Fluorescence and Improved Stability for Theranostic Applications

Abstract

It has been found that the self-assembly of nonfluorescent peptides can generate fluorescent peptide nanoparticles (f-PNPs) to perform multiple functions, including drug delivery and imaging and tracking therapeutic agents. Both pharmacologically inactive peptides and tumor-targeting peptides have been explored to construct biocompatible f-PNPs; however, the application of this technology in delivering antitumor peptides has never been reported. Herein, the self-assembly of an antitumor dipeptide, carnosine, into fluorescent carnosine nanoparticles (f-Car NPs) in the presence of zinc ions is demonstrated. The generated f-Car NPs exhibit fluorescence in the visible and near-infrared (NIR) ranges for fluorescence tracing in vitro and in vivo. On the other hand, the f-Car NPs minimize the contact between the dipeptide and the serum, which overcomes the dipeptide instability resulted from inefficient antitumor activity. In addition, the preparation of f-Car NPs does not introduce extra carrier materials, so the f-Car NPs exhibit biocompatibility to normal fibroblast cells in vitro and negligible toxicity against major organs in vivo. This study provides a new peptide drug delivery strategy with NIR fluorescence tracing ability.

Magnetically Controlled Nanorobots Based on Red Emissive Peptide Dots and Artificial Antibodies for Specific Recognition and Smart Scavenging of Nε-(Carboxymethyl)lysine in Dairy Products

“…Histidine has greatly been considered a critical building block to designing biology-related nanostructures because of the unique imidazole ring among 20 naturally occurring amino acids. Based on the introduction of Zn­(II), the self-assembling peptides-based nanostructure limited fluorophore mobility and reduced energy dissipation. , Therefore, three histidine-containing linear dipeptides including HH, FH, and AH and consequently cyclic dipeptides (CHH, CFH, and CAH) were used for chelation with Zn­(II) to investigate the fluorescence property. The fluorescence contour profiles of histidine-containing linear/cyclic dipeptides are displayed in Figure .…”

Dynamic responsiveness of self‐assembling peptide‐based nano‐drug systems

“…Various enzymes determine the functional diversity of enzyme-responsive PDCs, including alkaline phosphatase (ALP) (Figure 2A), 96,97 matrix metalloproteinases (MMPs), 98 and esterase, 99 amongst others. [100][101][102][103] In addition to enzyme regulation, the controllability of diverse peptide-based drug carrier construction has been explored by modulating individual microenvironment characteristics (e.g., pH, 104,105 ion concentration, 106 temperature, 107 or redox reactions 108,109 ) to influence the assembly state. 92,[110][111][112] However, exploring the role of individual factors in regulating peptide scaffold-based nano-drug systems has not contributed significantly to the need for personalized precision medicine.…”

Amino-Acid-Encoded Supramolecular Self-Assembly Architectures: Near-Infrared Fluorescence–Photothermal Temperature Dual-Signal Sensing of Hydrogen Peroxide

“…30,31 In addition, π−π stacking interactions occurring either among different imidazoles of histidine or the side-chain indole rings of tryptophan, which act as the driving force for the self-assembly process, tend to reduce the excited-state energy of the self-assembler and increase the fluorescence excitation and emission wavelengths. 32,33 Thus, with the advantage of peptides as typical molecularly encoded structural units, 34,35 rational tailoring of nanostructures, precise control of energy conversion pathways, and ultimately improving the multifunctionality of selfassembled peptide architectures are forthcoming.…”

“…This is unfavorable for the development of multifunctional materials that can simultaneously exhibit excellent fluorescence–photothermal multiple signatures. Delightfully, the photophysical properties of such self-assemblers depend mainly on the molecular organization of the building blocks, which are highly controlled by noncovalent interactions. , For example, when highly simplified linear dipeptides are used as building blocks alongside nonpigmented biomolecules, compared to controls in which the carboxyl groups are blocked by C-terminal amidation, diphenylalanine (H–Phe–Phe–OH, FF)-based conjugates weaken the contribution of hydrophobicity and hydrogen bonding due to the presence of two carboxyl groups that are deprotonated in biological conditions, which inhibits the stability of the self-assemblers and thus results in lower scattered light intensity. , In addition, π–π stacking interactions occurring either among different imidazoles of histidine or the side-chain indole rings of tryptophan, which act as the driving force for the self-assembly process, tend to reduce the excited-state energy of the self-assembler and increase the fluorescence excitation and emission wavelengths. , Thus, with the advantage of peptides as typical molecularly encoded structural units, , rational tailoring of nanostructures, precise control of energy conversion pathways, and ultimately improving the multifunctionality of self-assembled peptide architectures are forthcoming.…”