Springer eBooks, Год журнала: 2023, Номер unknown, С. 83 - 94
Опубликована: Янв. 1, 2023
Язык: Английский
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116910 - 116910
Опубликована: Июнь 8, 2024
Therapeutic proteins provided new opportunities for patients and high sales volumes. However, they are formulated extracellular targets. The lipophilic barrier of the plasma membrane renders vast array intracellular targets out reach. Peptide-based delivery systems, namely cell-penetrating peptides (CPPs), have few safety concerns, low immunogenicity, with control over administered doses. This study investigates CPP-based protein systems by classifying them into CPP-protein "covalent conjugation" CPP: "non-covalent complexation" categories. Covalent conjugates ensure proximity CPP to cargo, which can improve cellular uptake endosomal escape. We will discuss various aspects covalent through non-cleavable (stable) or cleavable bonds. Non-cleavable produced recombinant DNA technology express complete fusion in a host cell chemical ligation protein, ensures stability during process. bonds classified pH-sensitive redox-sensitive bonds, enzyme-cleavable physical stimuli linkers (light radiation, ultrasonic waves, thermo-responsive). highlighted key characteristics non-covalent complexes electrostatic hydrophobic interactions preserve conformational integrity cargo. CPP-mediated complexation, such as zippers, adaptor methods, avidin-biotin technology, featured. Conclusively, complexation methods appropriate when number samples be screened. In contrast, biological activity is critical compartment, conjugation protocols preferred.
Язык: Английский
Процитировано
14
South African Journal of Botany, Год журнала: 2024, Номер 169, С. 464 - 485
Опубликована: Май 4, 2024
Язык: Английский
Процитировано
11
Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102680 - 102680
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
2
Pharmaceuticals, Год журнала: 2024, Номер 17(2), С. 201 - 201
Опубликована: Фев. 2, 2024
The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance on list top ten threats global health. Immunomodulatory peptides that target a pathogen modulate immune system simultaneously are promising for development preventive therapeutic molecules. Since investigating innate immunity in insects has led prominent achievements human immunology, such as toll-like receptor (TLR) discovery, we used capacity immunomodulatory arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short sequences encrypted 643 from 55 foe-to-friend arthropods. critical features involved efficacy safety were calculated. Finally, 76 safe immunomodulators identified. Then, molecular docking simulation studies defined most optimal peptide ligands among all cell-surface TLRs. SPalf2-453 crab cell-penetrating immunoadjuvant antiviral properties. interacts TLR1/2 heterodimer. SBsib-711 blackfly TLR4/MD2 ligand cancer immunoadjuvant. In addition, binds CD47 PD-L1 tumor cells, which applicable immunotherapy checkpoint inhibitor. MRh4-679 shrimp broad-spectrum universal putative Th1/Th2-balanced response. We also implemented pathway enrichment analysis define fingerprints immunological signatures further vitro vivo immunogenicity reactogenicity measurements. Conclusively, combinatorial learning, docking, studies, well systems biology, open new opportunity multifunctional prophylactic lead peptides.
Язык: Английский
Процитировано
9
Biomaterials Advances, Год журнала: 2024, Номер 162, С. 213903 - 213903
Опубликована: Май 24, 2024
Язык: Английский
Процитировано
8
International Immunopharmacology, Год журнала: 2024, Номер 142, С. 113130 - 113130
Опубликована: Сен. 14, 2024
Язык: Английский
Процитировано
7
Biotechnology Advances, Год журнала: 2025, Номер unknown, С. 108545 - 108545
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
1
Bulletin du Cancer, Год журнала: 2023, Номер 110(12), С. 1288 - 1300
Опубликована: Окт. 9, 2023
Язык: Английский
Процитировано
16
Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Окт. 19, 2024
Scorpion venom may include pharmacological substances that have the potential to provide benefits. Multiple scientific investigations shown particular scorpion venoms induce apoptosis and inhibit development of cancerous cells. The present study investigated anticancer properties crude derived from Hottentotta saulcyi (H. saulcyi) on both in vivo mice models vitro breast carcinoma scorpions belonging species H. was obtained with application electrical stimulation at voltages 8 10 V. determination Average Lethal Dose 50 (LD50) conducted. work assessed cytotoxicity morphological characteristics using fluorescence microscopy, MTT assay, flow cytometry assessment. Additionally, research performed assess cytotoxic effects a mouse model cancer. examination MCF-7 cells treated microscopic level revealed existence undergoing apoptosis. has properties, as by observation had 62.12% apoptotic rate when exposed dose 1.47 mg/L. Based results obtained, it can be viability exhibited substantial reduction (P < 0.01). Furthermore, findings indicated resulted significant increase synthesis TNF-α, IL-6, IL-10, TGF-β, caspase 0.05). treatment groups administered augmentation expression proapoptotic genes compared control group healthy individuals. transcription BCL2 gene statistically venom-treated 0.05) malignant considerable promise demonstrating properties. Further investigation warranted explore medicinal platform for prevention
Язык: Английский
Процитировано
5
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115292 - 115292
Опубликована: Авг. 11, 2023
Patients receiving high-dose methotrexate (HDMTX) for malignancies are exposed to diverse complications, including nephrotoxicity, hepatotoxicity, mucositis, myelotoxicity, neurological symptoms, and death. Glucarpidase is a recombinant carboxypeptidase G2 (CPG2) that converts MTX into nontoxic metabolites. In this study, the role of vector type, gene optimization, orientation, host on expression CPG2 investigated. The effectiveness various therapeutic regimens containing glucarpidase classified perspectives dose adjustment based precision medicine provided. Conjugation with cell-penetrating peptides, human serum albumin, polymers such as PEG dextran delivery, higher stability, production biobetter variants highlighted. F(ab՜)2 or scFv antibody fragments against tumor-specific antigens corresponding prodrugs tumor-targeted drug delivery using antibody-directed enzyme prodrug therapy (ADEPT) communicated. Trials reduce off-target effects possibility repeated ADEPT cycles by adding pro-domains sensitive tumor-overexpressed proteases, antiCPG2 antibodies, mutants immune-system-unrecognizable epitopes, protective reported. Intracellular cpg2 gene-directed (GDEPT) concerns regarding safety transfection efficacy GDEPT vectors described. A novel bifunctional platform engineered CAR-T cell micropharmacies, known Synthetic Enzyme-Armed KillER (SEAKER) cells, expressing activate at tumor niche introduced. Taken together, integrated data in review recruiting combinatorial strategies systems define future directions ADEPT, GDEPT, SEAKER placement therein.
Язык: Английский
Процитировано
9