The healing of osteochondral defects (OCDs) that result from injury, osteochondritis, or osteoarthritis and bear lesions in the cartilage and bone, pain, and loss of joint function in middle- and old-age individuals presents challenges to clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage separately; however, none of them addressed the simultaneous healing of these tissues in the complicated heterogeneous environment of the osteochondral (OC) interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OCDs utilizing bone and cartilage-specific peptides should be examined and investigated. The main goal of this review was to study how they contribute to the healing of OCDs, either alone or in conjunction with other peptides and biomaterials.

Growth factors play a pivotal role in orchestrating cellular growth and division by binding to specific cell surface receptors. Dysregulation of growth factor production or activity can contribute to the uncontrolled cell proliferation observed in cancer. Peptide-based nanoformulations (PNFs) have emerged as promising therapeutic strategies for growth factor-deficient cancers. PNFs offer multifaceted capabilities including targeted delivery, imaging modalities, combination therapies, resistance modulation, and personalized medicine approaches. Nevertheless, several challenges remain, including limited specificity, stability, pharmacokinetics, tissue penetration, toxicity, and immunogenicity. To address these challenges and optimize PNFs for clinical translation, in-depth investigations are warranted. Future research should focus on elucidating the intricate interplay between peptides and nanoparticles, developing robust spectroscopic and computational methodologies, and establishing a comprehensive understanding of the structure-activity relationship governing peptide-nanoparticle interactions. Bridging these knowledge gaps will propel the translation of peptide-nanoparticle therapies from bench to bedside. While a few peptide-nanoparticle drugs have obtained FDA approval for cancer treatment, the integration of nanostructured platforms with peptide-based medications holds tremendous potential to expedite the implementation of innovative anticancer interventions. Therefore, growth factor-deficient cancers present both challenges and opportunities for targeted therapeutic interventions, with peptide-based nanoformulations positioned as a promising avenue. Nonetheless, concerted research and development endeavors are essential to optimize the specificity, stability, and safety profiles of PNFs, thereby advancing the field of peptide-based nanotherapeutics in the realm of oncology research.

Pollution caused by Copper and hydrogen sulfide pollution has severe adverse effects on the environment and organisms. Real-time, fast and accurate monitoring of Cu2+ and S2- faces serious challenges. In this study, we designed a novel biosensor and synthesized it by mimicking the structure of the main Cu(II)-binding site on bovine serum albumin. As a peptide-based sensor, FGGH (FITC-Gly-Gly-His-NH2) can perform the sequential detection of Cu2+ and S2- by fluorescence and colorimetry. The high water solubility and selectivity make it suitable for monitoring Cu2+ and S2- in environmental water samples with high sensitivity; its limit of detection (LOD) is as low as 1.42 nM for Cu2+ and 22.2 nM for S2-. The paper-based sensing platform of this probe was found to be a promising tool for the on-site visualization of real-time quantitative analysis of Cu2+ and S2- due to its rapid response and recyclable detection characteristics. Additionally, FGGH was successfully used to image Cu2+ and S2- in living cells and zebrafish models with adequate fluorescence stability and low cytotoxicity, providing the first visual evidence of the effect of the interactions between Cu2+ and S2- on the redox homeostasis of organisms.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering.

Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide-drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed.

The application of peptide-based biomaterials in nanocarriers can effectively reduce toxicity and improve the biocompatibility. In our study, a dual stimuli-responsive peptide-based drug delivery system was designed and synthesized, which was nontoxic and achieved the chem-photothermal therapy synergistic effect. Lanreotide (Lan), a kind of somatostatin analogue, was used as internal template to prepared lychee-shaped palladium (Pd) nanoparticles (Lan-PdNPs). Glutathione (GSH) and doxorubicin (DOX) were combined on the surface of Lan-PdNPs to obtain the nanosystem of Lan-PdNPs@GSH/DOX. Based on the lychee-shaped structures, the system demonstrated higher photothermal conversion performance and photothermal stability. Under NIR laser irradiation, Lan-PdNPs@GSH/DOX could convert light energy to heat in effect and accelerate drug release. Moreover, in acidic conditions, the system also exhibited the pH-responsive drug release. Owing to the synergism, the antitumor effects of Lan-PdNPs@GSH/DOX in vitro and in vivo were superior, and the inhibition ratio was much higher than that of chemotherapy or photothermal therapy alone. The good biocompatibility and nontoxicity of the system also provide the possibility for serving as an antitumor drug candidate.

To understand the molecular interactions, present in living organisms and their environments, chemists are trying to create novel chemical tools. In this regard, peptide-based fluorescence techniques have attracted immense interest. Synthetic peptide-based fluorescent probes are advantageous over protein-based sensors, since they are synthetically accessible, more stable, and can be easily modified in a site-specific manner for selective biological applications. Peptide receptors labeled with environmentally sensitive/FRET fluorophores have allowed direct detection/monitoring of biomolecules in aqueous media and in live cells. In this review, key peptide-based approaches for different biological applications are presented.

BACKGROUND: Malnutrition affects 50% of hospitalized children and 25-70% of critically ill children. Enteral tube feeding is generally considered the preferred modality for critically ill pediatric patients. Clinical advantages of using peptide-based formulas are still controversial in critically ill children. The aim of this study was to compare the effect of a peptide-based formula versus a standard polymeric formula on feeding tolerance and whether this will affect the outcome among critically ill children.
METHODS: This single blind case control study was conducted on 180 randomly selected critically ill children in the pediatric critical care unit (PICU) of Ain Shams University. Patients were divided into 2 groups: a group receiving a standard polymeric formula (group 1; 90 patients) and a group receiving a peptide-based formula (group II; 90 patients). Nutritional requirements, days to reach full enteral feeding, feeding intolerance symptoms and anthropometric measurements were recorded for all patients at admission together with their pediatric risk of mortality score (PRISM). Length of PICU stay, occurrence of sepsis together with survival were analyzed at discharge as outcome measures.
RESULTS: Patients receiving a peptide-based formula showed a significant decrease in feeding interruptions and abdominal distention (p < 0.000), reached full enteral feeding faster (2.60 ±0.74 days versus 5.36 ±1.00 days in patients received polymeric standard formula; p < 0.001) and improved weight gain (p < 0.028). Moreover, duration of sepsis was significantly shorter (p < 0.045), but no difference in mortality was recorded between patient groups.
CONCLUSIONS: Peptide-based formula feeding was better tolerated than standard polymeric formula feeding in critically ill pediatric patients. However, the choice of patients receiving the peptide-based formula needs to be further evaluated.

For the past three decades, pharmaceutical research has been mainly converging to novel carrier systems and nanoparticulate colloidal technologies for drug delivery, such as nanoparticles, nanospheres, vesicular systems, liposomes, or nanocapsules to impart novel functions and targeting abilities. Such technologies opened the gate towards more sophisticated and effective multi-acting platform(s) which can offer site-targeting, imaging, and treatment using a single multifunctional system. Unfortunately, such technologies faced major intrinsic hurdles including high cost, low stability profile, short shelf-life, and poor reproducibility across and within production batches leading to harsh bench-to-bedside transformation.Currently, pharmaceutical industry along with academic research is investing heavily in bioconjugate structures as an appealing and advantageous alternative to nanoparticulate delivery systems with all its flexible benefits when it comes to custom design and tailor grafting along with avoiding most of its shortcomings. Bioconjugation is a ubiquitous technique that finds a multitude of applications in different branches of life sciences, including drug and gene delivery applications, biological assays, imaging, and biosensing.Bioconjugation is simple, easy, and generally a one-step drug (active pharmaceutical ingredient) conjugation, using various smart biocompatible, bioreducible, or biodegradable linkers, to targeting agents, PEG layer, or another drug. In this chapter, the different types of bioconjugates, the techniques used throughout the course of their synthesis and characterization, as well as the well-established synthetic approaches used for their formulation are presented. In addition, some exemplary representatives are outlined with greater emphasis on the practical tips and tricks of the most prominent techniques such as click chemistry, carbodiimide coupling, and avidin-biotin system.