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Cys-Arg-Glu-Lys-Ala (CREKA) is an important fibrin-homing pentapeptide that has been extensively demonstrated for diagnoses and therapies (e.g., image diagnosis of tumors and to inhibit tumor cell migration and invasion). Although CREKA-loaded nanoparticles (NPs) have received major interest as efficien biomedical systems for cancer diagnosis and treatment, almost no control on the peptide release has been achieved yet. Herein, we report the development of conductive polymer NPs as therapeutic CREKA carriers for controlled dose administration through electric stimuli. Furthermore, the study was extended to CR( N Me)EKA, a previously engineered CREKA analogue in which Glu was replaced by N -methyl-Glu for improvement of the peptide resistance against proteolysis, which is one of the major weaknesses of therapeutic peptide delivery, and for enhancement of the tumor homing capacity by overstabilizing the bioactive conformation. Particularly, the present work is focused on understanding the interactions between the newly designed nanoengineered materials and biological fluids and the achievement of a modulated peptide release by fine-tuning the electrical stimuli . Two different types of stimuli were compared, chronoamperometry versus cyclic voltammetry, the latter being more effective.

acs biomaterials science and engineering

Encapsulation and Storage of Therapeutic Fibrin-Homing Peptides using Conducting Polymer Nanoparticles for Programmed Release by Electrical Stimulation