Recent advances of CREKA peptide-based nanoplatforms in biomedical applications

Abstract

Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed.

A thiol–ene mediated approach for peptide bioconjugation using ‘green’ solvents under continuous flow

“…48 Conjugation of CREKA peptide 22 has primarily been utilised to facilitate the imaging of cancer cells, typically via maleimide conjugation at the Cys residue of the peptide. 49 CREKA peptide 22 represents an ideal model substrate for aqueous radical mediated thiol-ene bioconjugation due to the presence of a terminal Cys residue and aqueous solubility. Allylated monosaccharide 6 was selected as the alkene component of the reaction as glycoconjugates of CREKA peptide 22 have not previously been reported in the literature and may be of considerable importance for biological applications due to the unique properties of glycoconjugates including cell uptake and lectin binding.…”

Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution

“…To precisely deliver the drug to the kidney tissue and act on the ER of macrophages, fibrillar targeting peptide cysteine−arginine− glutamic acid−lysine−alanine (CREKA, C5) was introduced to specifically recognize the highly expressed fibronectin in the diseased kidney of UUO model mice to achieve tissue targeting to the kidney. 39,40 Nanoemulsion is subsequently identified and endocytosed by abundant macrophages (Scheme S1A−D), after which its precise delivery in the ER fraction of cells can be achieved with the help of ER target molecules DSPE-PEG-Pardaxin. 41−43 And the drug is released in response to high intracellular ROS levels (Scheme S1E).…”

“…With the help of the reduction response characteristics of α-TOS, the responsive release of drugs in an inflammatory environment could be achieved (Scheme A). To precisely deliver the drug to the kidney tissue and act on the ER of macrophages, fibrillar targeting peptide cysteine–arginine–glutamic acid–lysine–alanine (CREKA, C5) was introduced to specifically recognize the highly expressed fibronectin in the diseased kidney of UUO model mice to achieve tissue targeting to the kidney. , Nanoemulsion is subsequently identified and endocytosed by abundant macrophages (Scheme S1A–D), after which its precise delivery in the ER fraction of cells can be achieved with the help of ER target molecules DSPE-PEG-Pardaxin. − And the drug is released in response to high intracellular ROS levels (Scheme S1E). , The combination of nanotechnology-based small molecule inhibitors and precise delivery of traditional anti-inflammatory drugs can achieve the effective modulation of diseased tissue macrophages.…”

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis

“…Hydrophobic molecules can be encapsulated in the hydrophobic core of self-assembled amphiphilic peptide nanocarriers. 33,34 By combining the ability of the CREKA peptide to target fibrin-rich microthrombi within the tumor with the passive targeting effect of the EPR, 35,36 greater accumulation of peptide-based nanocarriers at the tumor site can be achieved. ALP induced a trans-formation in the nanoparticle morphology to generate aggregates with a high aspect ratio.…”

“…Here, based on our previous research, − we designed a drug delivery system, PD/Pep1, consisting of an amphiphilic peptide (Pep1) containing the peptide Cys-Arg-Glu-Lys-Ala (CREKA) carrying the chemotherapeutic drug paclitaxel (PTX) and the antiplatelet drug DIP. Hydrophobic molecules can be encapsulated in the hydrophobic core of self-assembled amphiphilic peptide nanocarriers. , By combining the ability of the CREKA peptide to target fibrin-rich microthrombi within the tumor with the passive targeting effect of the EPR, , greater accumulation of peptide-based nanocarriers at the tumor site can be achieved. ALP induced a transformation in the nanoparticle morphology to generate aggregates with a high aspect ratio.…”