Current Pharmaceutical Design - Volume 29, Issue 9, 2023

The self-assembly of peptides is very popular in biomedical fields. Peptide-based assemblies have been used as an ideal candidate for drug/gene delivery, tissue engineering, and antibacterial/anticancer agents. The morphology and structure of peptide self-assembly can be changed by altering the molecular structure and the self-assembly conditions. Engineering peptide assemblies present great potential in medical fields. In this review, the structure and function of peptide self-assembly have been described. Also, the advances in peptide- based self-assembly have been highlighted in biomedical applications, such as drug packaging and delivery, tissue engineering, antibacterial agents, siRNA-targeted delivery and vaccines. Moreover, the challenges and future perspectives of the self-assembly of polypeptides are discussed.

Bioactive peptides are specific protein fragments that prove health-promoting potential for humans. The bioactivities include antimicrobial, antioxidant, anticancer, immunomodulatory activities, etc. Hence, bioactive peptides' production technology and processes have attracted excessive attention, especially concerning peptides' synthesis, separation, identification, and functionality. This review summarizes the relevant investigations from the above four aspects. Among the production technology of bioactive peptides, biosynthesis, chemosynthesis, technology for separation and purification, and the interactions responsible for peptide-based nanostructures are emphasized. Here, the biosynthesis of peptides includes enzymatic hydrolysis, microbial fermentation, and recombinant DNA technology, and chemosynthesis consists of solution-phase peptide synthesis and solid-phase peptide synthesis (SPPS). The commonly used enzymes in enzymatic hydrolysis are investigated, including pepsin, trypsin, and alcalase. The commonly used microorganisms, typical processes, protein sources, and advantages of microbial fermentation are analyzed. Membrane separation (including ultrafiltration and nanofiltration), chromatography technology (including ion-exchange chromatography, gel filtration chromatography, affinity chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC)), and electrophoresis technology are detailed for the purification technology. Mass spectrometry (MS), its combination with the high-performance separation method, and nuclear magnetic resonance (NMR) are elucidated for the identification technology. The non-covalent interactions responsible for peptide-based nanostructures involve electrostatic force, hydrogen bonds, π-π stacking, hydrophobic interaction, and van der Waals force. Afterward, we detail the peptides' antihypertensive, antithrombotic, anticancer, antimicrobial, antioxidant, and immunomodulatory activities. The activity analysis mainly involves peptides' sources, structural features, mechanisms of action, and influencing factors. Based on the production and functionality elucidation, potential challenges for peptide application in biomedicine are given. The challenge is analyzed from the aspects of purification and identification technologies and influencing factors of peptides' bioactivities. Our work will elaborate on advances in the production technology of peptides and their bioactivities, which could promote and expand their industrial applications.

Background: The antioxidant properties of active peptides from silkworm pupae protein hydrolysate are of interest, and it serves as a novel source of calcium supplement. Methods: Optimize the preparation parameters of silkworm pupae bioactive peptide-calcium chelate, and investigate the mechanism and bioavailability of silkworm pupae active peptide as a transport carrier to promote calcium ion absorption using simulated gastrointestinal digestion and Caco-2 monolayer cell model. Results: The optimal process parameters for preparing peptide calcium chelate were the peptide calcium mass ratio of 3:1, pH of 6.7, a temperature of 35.6°C, and time of 32.8 min by Box-Behnken design, and the calciumchelating rate reached 84.67%. The DPPH radical scavenging activity of silkworm pupae protein hydrolysatecalcium chelate was 79.36 ± 4.31%, significantly higher than silkworm pupae protein hydrolysate (61.00 ± 9.56%). Fourier transform infrared spectroscopy shows that the COO-, N-H, C-H, and C-O groups participated in the formation of silkworm pupae protein hydrolysate-calcium chelate. The particle size of the silkworm pupae protein hydrolysate-calcium chelate was 970.75 ± 30.12 nm, which was significantly higher than that of silkworm pupae protein hydrolysate (253.14 ± 5.72 nm). The silkworm pupae protein hydrolysate-calcium chelate showed a calcium dissolution rate of 71.01 ± 1.91% in the simulated intestinal phase, significantly higher than that of CaCl2 (59.34 ± 1.24%). In the Caco-2 cell monolayers, the silkworm pupae protein hydrolysatecalcium chelate was more favorable for calcium transport. Conclusion: A novel silkworm pupa protein hydrolysate-calcium chelate with high antioxidant activity was successfully prepared to improve the bioavailability of calcium.

This study aims to develop a novel tumor-targeted molecular probe for pancreatic cancer imaging. The objective of this is to prepare a CKAAKN peptide-conjugated poly (lactic-co-glycolic acid)-poly (ethylene glycol) amphiphilic polymer (CKAAKN-PEG-PLGA) for the tumor-targeted delivery of magnetic resonance imaging (MRI) contrast agent ultrasmall superparamagnetic iron oxide (USPIO). Background: The early diagnosis of pancreatic cancer is crucial for improving its prognosis, but the clinical application of many diagnostic methods is limited owing to a lack of specificity and sensitivity. Methods: CKAAKN-PEG-PLGA was synthesized by the amidation reaction. USPIO-loaded polymeric magnetic nanoparticles (USPIO@CKAAKN-PEG-PLGA) were prepared by the emulsion solvent evaporation method. The in vitro tumor targeting and bio-safety of nanoparticles were evaluated by targeted cellular uptake, MR imaging and MTT assay. Results: USPIO@CKAAKN-PEG-PLGA nanoparticles showed excellent biosafety with an average diameter of 104.5 ± 4.1 nm. Modification of CKAAKN peptide could improve USPIO binding ability to internalize into CKAAKN-positive BxPC-3 cells compared with non-targeting nanoparticles and the control group. The relative fluorescence intensity in BxPC-3 and HPDE6-C7 cells was 23.77 ± 4.18 and 6.44 ± 2.10 (p < 0.01), and respectively became 16.13 ± 0.83 and 11.74 ± 1.74 after the addition of free CKAAKN peptide. In vitro MR imaging studies showed that an obvious decrease in the signal intensity was observed in the targeted nanoparticles group incubated with BxPC-3 and HPDE6-C7 cells (p < 0.05). Conclusion: USPIO@CKAAKN-PEG-PLGA nanoparticles could significantly enhance the tumor specificity of USPIO in CKAAKN-positive pancreatic cancer cell BxPC-3, which is expected as a promising candidate of MRI contrast enhancement for the early diagnosis of pancreatic cancer.

Background: Cancer is an ailment with having a very low survival rate globally. Poor cancer prognosis is primarily caused by the fact that people are found to have the disease when it is already well advanced. The goal of this study is to compile information on new avenues of investigation into biomarkers that may facilitate the routine detection of cancer. Proteomic analysis has recently developed into a crucial technique for cancer biology research, working in tandem with genomic analysis. Mass spectrometry techniques are one of several proteome analysis techniques that allow for the highly precise quantitative and qualitative recognition of hundreds of proteins in small quantities from various biological materials. These findings might soon serve as the foundation for better cancer diagnostic techniques. Methods: An exhaustive literature survey has been conducted using electronic databases such as Google Scholar, Science Direct, and PubMed with keywords of proteomics, applications of proteomics, the technology of proteomics, biomarkers, and patents related to biomarkers. Result: Studies reported till 2021 focusing on cancer proteomics and the related patents have been included in the present review to obtain concrete findings, highlighting the applications of proteomics in cancer. Conclusion: The present review aims to present the overview and insights into cancer proteomics, recent breakthroughs in proteomics techniques, and applications of proteomics with technological advancements, ranging from searching biomarkers to the characterization of molecular pathways, though the entire process is still in its infancy.

Introduction: Diabetic osteoporosis (DOP) has gradually gained public attention. The clinical manifestations of DOP include bone mass loss, bone microstructural damage, and increased bone fragility. Methods: Intracellular reactive oxygen species (ROS) production was significantly increased under high glucose (HG) conditions, with deleterious effects on bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Vitamin K2 (VK2) has been demonstrated to promote bone formation both in vitro and in vivo. Results: However, its potential role in diabetes-induced osteoporosis remains unelucidated. This study aims to verify whether VK2 treatment could relieve the deleterious effects of high glucose on BMSCs and delay the progression of osteoporosis. The results revealed that the HG environment downregulated the expression of osteogenesis- related proteins. Conclusion: Correspondingly, VK2 treatment reversed the osteogenic phenotype of BMSCs under HG conditions. In addition, using an established diabetes-induced osteoporosis rat model, we found that VK2 administration could restore bone mass and microstructure. In conclusion, our results provide a promising therapeutic option in the clinical treatment of DOP.