1. Lipid-mimicking peptide decorates erythrocyte membrane for active delivery to engrafted MDA-MB-231 breast tumour.
- Author
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Fan X, Xu H, Zhao F, Song J, Jin Y, Zhang C, and Wu G
- Subjects
- Animals, Cell Line, Cell Line, Tumor, Doxorubicin chemistry, Drug Delivery Systems methods, Female, HEK293 Cells, Humans, Hydrophobic and Hydrophilic Interactions, Lipid Bilayers chemistry, Liposomes chemistry, Mice, Mice, Inbred BALB C, Mice, Nude, Xenograft Model Antitumor Assays, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Erythrocyte Membrane chemistry, Erythrocyte Membrane drug effects, Lipids chemistry, Peptides chemistry
- Abstract
Decorating the membrane surface of vesicle carriers with proteins for targeted delivery has been achieved mainly by chemical methods. In this study, we report the rational design of a lipid-mimicking peptide for biomembrane decoration without chemical conjugation. A peptide Pm45 consisting of a hydrophobic helical tail and an anionic headgroup linked with an integrin-targeting RGD moiety was manually designed. Pm45 was synthesized and characterized, which confirmed an alpha-helix at the C-terminal. Pm45 spontaneously intercalated into the lipid bilayer as illustrated by quartz crystal of microbalance with dissipation (QCM-D), a calcein leakage assay, and TEM. The intercalation was accomplished within 10 min, and the ITC results indicated that the affinity of Pm45 binding with lipids was ~100-fold greater than that of the naturally occurring cell-penetrating peptide Ib-AMP4. In vitro cellular experiments indicated that the Pm45-decorated erythrocyte vesicles specifically bound and killed integrin αvβ3-expressing MDA-MB-231 breast cancer cells. The targeting potential of Pm45-decorated erythrocyte vesicles was further evaluated in an MDA-MB-231 xenograft nude mouse model. The in vivo therapeutic effects indicated that the targeting vesicles significantly improved the therapeutic effect of encapsulated doxorubicin (DOX) compared with that of DOX or non-targeting vesicles. NIRF imaging implied that the targeting vesicles improved the pharmacokinetics of DOX in vivo and concentrated DOX in the tumour tissue at levels >50% higher than those achieved by non-targeting liposomes. This study reports a new method for liposome decoration as an alternative to chemical conjugation., Competing Interests: Declaration of Competing Interest We declare of no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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