Efficient Transdermal Delivery of Functional Protein Cargoes by a Hydrophobic Peptide MTD 1067

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jun 27

PMID 35760980

Authors

Hee Je Shin

Sun Uk Bak

Ha Na La

Jin Sun Kang

Hwa Hyun Lee

Hyo Jung Eom

Byung Kyu Lee

Hyun Ah Kang

Affiliations

Soon will be listed here.

Abstract

The skin has a protective barrier against the external environment, making the transdermal delivery of active macromolecules very difficult. Cell-penetrating peptides (CPPs) have been accepted as useful delivery tools owing to their high transduction efficiency and low cytotoxicity. In this study, we evaluated the hydrophobic peptide, macromolecule transduction domain 1067 (MTD 1067) as a CPP for the transdermal delivery of protein cargoes of various sizes, including growth hormone-releasing hexapeptide-6 (GHRP-6), a truncated form of insulin-like growth factor-I (des(1-3)IGF-I), and platelet-derived growth factor BB (PDGF-BB). The MTD 1067-conjugated GHRP-6 (MTD-GHRP-6) was chemically synthesized, whereas the MTD 1067-conjugated des(1-3)IGF-I and PDGF-BB proteins (MTD-des(1-3)IGF-I and MTD-PDGF-BB) were generated as recombinant proteins. All the MTD 1067-conjugated cargoes exhibited biological activities identical or improved when compared to those of the original cargoes. The analysis of confocal microscopy images showed that MTD-GHRP-6, MTD-des(1-3)IGF-I, and MTD-PDGF-BB were detected at 4.4-, 18.8-, and 32.9-times higher levels in the dermis, respectively, compared to the control group without MTD. Furthermore, the MTD 1067-conjugated cargoes did not show cytotoxicity. Altogether, our data demonstrate the potential of MTD 1067 conjugation in developing functional macromolecules for cosmetics and drugs with enhanced transdermal permeability.

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References

Derivery E, Bartolami E, Matile S, Gonzalez-Gaitan M . Efficient Delivery of Quantum Dots into the Cytosol of Cells Using Cell-Penetrating Poly(disulfide)s. J Am Chem Soc. 2017; 139(30):10172-10175. PMC: 5553715. DOI: 10.1021/jacs.7b02952. View

He H, Ye J, Wang Y, Liu Q, Chung H, Kwon Y . Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application. J Control Release. 2013; 176:123-132. PMC: 3939723. DOI: 10.1016/j.jconrel.2013.12.019. View

Cosgrave L, Devocelle M, Forster R, Keyes T . Multimodal cell imaging by ruthenium polypyridyl labelled cell penetrating peptides. Chem Commun (Camb). 2009; 46(1):103-5. DOI: 10.1039/b918611e. View

Jeon D, Kim S, Chetana M, Jo D, Ruley H, Lin S . Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat Neurosci. 2010; 13(4):482-8. PMC: 2958925. DOI: 10.1038/nn.2504. View

Oehlke J, Scheller A, Wiesner B, Krause E, Beyermann M, Klauschenz E . Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. Biochim Biophys Acta. 1998; 1414(1-2):127-39. DOI: 10.1016/s0005-2736(98)00161-8. View

Gallo M, Defaus S, Andreu D . 1988-2018: Thirty years of drug smuggling at the nano scale. Challenges and opportunities of cell-penetrating peptides in biomedical research. Arch Biochem Biophys. 2018; 661:74-86. DOI: 10.1016/j.abb.2018.11.010. View

Thevenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tuffery P . PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 2012; 40(Web Server issue):W288-93. PMC: 3394260. DOI: 10.1093/nar/gks419. View

Liu G, Liu L, Lin C, Tseng J, Chuang M, Lam H . Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: involvement of alpha-melanocyte-stimulating hormone-mediated inhibition of the nuclear factor kappaB/cyclooxygenase-2 pathway. Mol Pharmacol. 2005; 69(2):440-51. DOI: 10.1124/mol.105.015404. View

Deshayes S, Morris M, Divita G, Heitz F . Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci. 2005; 62(16):1839-49. PMC: 11139131. DOI: 10.1007/s00018-005-5109-0. View

10.

Morris M, Vidal P, Chaloin L, Heitz F, Divita G . A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Res. 1997; 25(14):2730-6. PMC: 146800. DOI: 10.1093/nar/25.14.2730. View

11.

Penalva A, Carballo A, Pombo M, Casanueva F, Dieguez C . Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. J Clin Endocrinol Metab. 1993; 76(1):168-71. DOI: 10.1210/jcem.76.1.8421084. View

12.

Van Asbeck A, Beyerle A, McNeill H, Bovee-Geurts P, Lindberg S, Verdurmen W . Molecular parameters of siRNA--cell penetrating peptide nanocomplexes for efficient cellular delivery. ACS Nano. 2013; 7(5):3797-807. DOI: 10.1021/nn305754c. View

13.

Yoon S, Kim K, Jo S, Cho A, Jeon S, Choi H . Induction of hair growth by insulin-like growth factor-1 in 1,763 MHz radiofrequency-irradiated hair follicle cells. PLoS One. 2011; 6(12):e28474. PMC: 3229574. DOI: 10.1371/journal.pone.0028474. View

14.

Veach R, Liu D, Yao S, Chen Y, Liu X, Downs S . Receptor/transporter-independent targeting of functional peptides across the plasma membrane. J Biol Chem. 2003; 279(12):11425-31. DOI: 10.1074/jbc.M311089200. View

15.

Gautier R, Douguet D, Antonny B, Drin G . HELIQUEST: a web server to screen sequences with specific alpha-helical properties. Bioinformatics. 2008; 24(18):2101-2. DOI: 10.1093/bioinformatics/btn392. View

16.

Brodsky J . Translocation of proteins across the endoplasmic reticulum membrane. Int Rev Cytol. 1997; 178:277-328. DOI: 10.1016/s0074-7696(08)62139-7. View

17.

Chaloin L, Vidal P, Heitz A, Van Mau N, Mery J, Divita G . Conformations of primary amphipathic carrier peptides in membrane mimicking environments. Biochemistry. 1997; 36(37):11179-87. DOI: 10.1021/bi9708491. View

18.

Ballard F, Wallace J, Francis G, Read L, Tomas F . Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol. 1996; 28(10):1085-7. DOI: 10.1016/1357-2725(96)00056-8. View

19.

Frankel A, Pabo C . Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988; 55(6):1189-93. DOI: 10.1016/0092-8674(88)90263-2. View

20.

Lin Y, Yao S, Veach R, Torgerson T, Hawiger J . Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J Biol Chem. 1995; 270(24):14255-8. DOI: 10.1074/jbc.270.24.14255. View