In that work, the disulfide bonds were randomly distributed along the polymeric chains. In a previous publication by our group, we presented the synthesis of disulfide crosslinked polypeptide nanogels consisting of PHis and PCys, which show satisfying pH, redox and thermo-responsiveness to the external stimuli. ![]() In both works, PCys was in a block form and a similar sustained release of the drug was observed. reported the synthesis of DOX-loaded and gold-embedded micelles based on poly( l-cysteine) which exhibit synergistic chemo- and photothermal therapy of cancer cells. A sustained release profile of DOX was observed from these NPs where the PCys was in a block form. managed to synthesize redox-responsive SCL micelles based on poly(ethylene glycol)- b-poly( l-cysteine)- b-poly( l-phenylalanine) triblock copolymers, which could load DOX. In the case of polypeptides bearing an amine or carboxylic acid in their side chains, pH changes activate the protonation/deprotonation mechanism, leading to the disassembly of their conformation and the desired triggered release of their cargo. Therefore, pH-responsive systems can induce controlled drug release and penetrate deeper into cancer cells, due to pH variations between the intracellular organelles of the cell and the extracellular matrix. The blood serum has a pH value of 7.4, while the endosomal and extracellular pH of the cancer tissues exhibits a pH range from 6.3–6.8, and that of the lysosomal compartments of the cell can be between pH 5.5–5.0. ![]() Usually, the pH value of a tumor tissue is 6.3–6.8, while higher concentrations of various biological substances are detected in cancer cells such as GSH and matrix metalloproteinase 2 (MMP2) as well as active oxidative species (ROS). The tumor microenvironment is dynamic and is characterized by acidity, hypoxia and ischemia. Ideally, smart drug delivery systems to target cancer cells should have the ability to bypass numerous biological obstacles such as vasculature and non-vasculature barriers and tumor microenvironment as well as intracellular barriers. Finally, in vitro cytotoxicity assay of the DOX-loaded NPs against three different breast cancer cell lines showed that the nanocarriers exhibited similar or slightly better activity as compared to the free drug, rendering these novel NPs very promising materials for drug delivery applications. It was found that the topology of PCys significantly altered the structure as well as the release profile of the NPs. ![]() The anticancer drug doxorubicin (DOX) was efficiently encapsulated in the hydrophobic core of the nanostructures and released under pH and redox conditions that simulate the healthy and cancer tissue environment. The ability of the synthesized polymers to mimic natural proteins was examined by Circular Dichroism (CD), while the study of zeta potential revealed the “stealth” properties of NPs. ![]() Moreover, the pH and redox responsiveness in the presence of the reductive tripeptide of glutathione (GSH) was investigated at the empty as well as the loaded NPs. Dynamic light scattering (DLS), static light scattering (SLS) and transmission electron microscopy (TEM) were utilized to obtain the structure of the NPs. Due to the presence of the thiol groups of PCys, a crosslinking process was achieved further stabilizing the nanoparticles (NPs) formed. These amphiphilic hybrid copolypeptides assemble in aqueous media to form micellar structures, comprised of an outer hydrophilic corona of PEO chains, and a pH- and redox-responsive hydrophobic layer based on PHis and PCys. The topology of PCys was either the middle block, the end block or was randomly distributed along the PHis chain. The synthesis of the terpolymers was achieved through a ring-opening polymerization (ROP) of the corresponding protected N-carboxy anhydrides of N im- Trityl- l-histidine and S- tert-butyl- l-cysteine, using an end-amine-functionalized poly(ethylene oxide) ( mPEO-NH 2) as macroinitiator, followed by the deprotection of the polypeptidic blocks. Τhe synthesis of a series of novel hybrid block copolypeptides based on poly(ethylene oxide) (PEO), poly( l-histidine) (PHis) and poly( l-cysteine) (PCys) is presented.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |