Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

Membrane-disruptive peptides/peptidomimetics(MDPs)are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes,in contrast to conventional chemotherapeutic drugs,which act on precise targets such as DNA or specific enzymes.Owing to their rapid action,broad-spectrum activity,and mechanisms of action that potentially hinder the development of resistance,MDPs have been increasingly considered as future therapeutics in the drug-resistant era.Recently,growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents.In this review,we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs,and summarize the current development and mechanisms of MDPs alone or in combination with other agents.Notably,this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs,minimize side effects,and promote the codelivery of multiple chemotherapeutics,for more efficient antimicrobial and anticancer therapy.

Combination of hydrophobically modified γ-poly(glutamic acid)and trehalose achieving high cryosurvival of RBCs

Trehalose is expected to be an alternative for toxic glycerol as a biocompatible cryoprotectant of red blood cells(RBCs).In this work,γ-poly(glutamic acid)(PGA)is modified by grafting hydrophobic phenethylamine,3,4-dimethoxyphenylethylamine and dodecylamine,respectively.The graft-modified PGA can significantly enhance cryosurvival of RBCs in combination with trehalose.Analyses of dynamic light scattering,hemolysis assay,atomic force microscope and confocal laser scanning microscope suggest that the modified PGA polymers can self-assemble into nanoparticles in phosphate buffer saline solutions at the pH range of 6.0–7.4,and exhibit membrane-disruptive activity due to hydrogen bond,conjugation and hydrophobic interactions with cell membranes.It is assumed that the modified PGA polymers can improve the cryosurvival of RBCs by promoting membrane permeability of trehalose.Among the three graft-modified polymers,phenethylamine-grafted PGA(PGA-g-PEA)can significantly increase the intracellular trehalose-loading content to 11.3±2.4 m M at pH 7.4,much higher than the value0.17±0.66 m M when trehalose is used without any polymers.In view of the aforementioned merit,the cryosurvival rate of sheep RBCs is increased to about 90%by incubation with 1.0 mg mL-1 PGA-g-PEA and 0.36 M trehalose.In vitro cell culture of L929 fibroblasts demonstrates low cytotoxicity of PGA-g-PEA.Therefore,hydrophobic PEA-modified PGA with enhanced intracellular trehalose-loading ability can be potentially applied in glycerol-free RBC cryopreservation or other related biomacromolecule delivery systems.