The consideration of indolicidin modification to balance its hemocompatibility and delivery efficiency.
Indolicidin (IL) is an antimicrobial peptide (AMP), which has been utilized as a cell penetrating peptide (CPP) for drug delivery. However, the hemolysis restricts its clinical application. Therefore, we investigated the delivery efficiency and hemocompatibility of IL and its derivatives. The transportation of fluorophore to NIH/3T3 cells could be improved either by in accompany with these peptides or in the form of peptide-conjugates. The hydrophobicity scales of these peptides were calculated according to their residues, which were compared to their effects on hemolysis as well as cell uptake efficiency. The results suggested that the cell penetrability of IL and its derivatives was related to their hydrophobicity scales based on the octanol-interface scale (ΔGoct-if), whereas their hemolysis levels depended on the hydrophobicity scales based on interface (ΔGwif). Consequently, we designed two peptides, IL-R57F89 and SAP10, to validate the correlation. These two peptides had similar ΔGwif; however, the ΔGoct-if of SAP10 was much higher than that of IL-K7F89. Both IL-R57F89 and SAP10 demonstrated extremely low hemolysis. Compared to the limit cell uptake of SAP10, IL-R57F89 greatly promoted the delivery efficiency. These results were consistent to our prediction, suggesting that hydrophobicity scales should be a useful preliminary guidance for AMP-derived CPP design.
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan.
Ching-Wei
CW
Tsai
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan. Electronic address: huweiwen@cc.ncu.edu.tw.
Wei-Wen
WW
Hu
Department of Nursing, Meiho University, Taiwan.
Chih-I
CI
Liu
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan; R&D Center for Membrane Technology, Department of Chemical Engineering, Chung Yuan Christian University, Taiwan.
Ruoh-Chyu
RC
Ruaan
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan.
Bing-Chang
BC
Tsai
Department of Life Sciences, National Central University, Taiwan.
Shiow-Lian Catherine
SL
Jin
R&D Center for Membrane Technology, Department of Chemical Engineering, Chung Yuan Christian University, Taiwan.
Yung
Y
Chang
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan.
Wen-Yih
WY
Chen
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000493:pharmacokinetics; D006461:Hemolysis / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D041681:NIH 3T3 Cells; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C073143:indolicidin; D016650:Fluorescein-5-isothiocyanate
Cell-penetrating peptide; Direct penetration; Hydrophobicity; Indolicidin; Transmembrane mechanism