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Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and β) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

CGKRK is a well-known tumor homing peptide with significant specificity for many types of cancer tissues. Herein, we describe the synthesis of a novel drug delivery system based on dextran decorated with myristoyl-ECGKRK peptide. The myristoylated peptide was synthesized and conjugated to dextran via an ester bond followed by purification. FT-IR and NMR confirmed the success of the conjugation reaction, while the surface morphology examination revealed that the conjugate has a characteristic porous network-like structure. Dynamic-light scattering measurements indicated the ability of the conjugate to self-assemble into nanoparticles with an average size of 248 ± 6.33 nm, and zeta potential of 10.7 mV. The cytotoxicity profiles for the peptide, dextran (Dex0), and dextran-peptide conjugate (Dex1) were evaluated against triple-negative breast cancer cells (MDA-MB-231), breast cancer cells (MCF-7), and human embryonic normal kidney cells (HEK-293). The results revealed that myristoyl-ECGKRK was noncytotoxic on the two different breast cancer cell lines up to 50 μM, but the cell viability was minimally reduced to 85% at 50 μm in HEK-293 cells. Similarly, Dex0 showed a neglected cytotoxicity profile at all tested concentrations. The Dex1 was not toxic to the cells up to a concentration of 8.3 mg/mL., (Copyright © 2021 Elsevier B.V. All rights reserved.)