Cell-Penetrating Peptide-Patchy Deformable Polymeric Nanovehicles with Enhanced Cellular Uptake and Transdermal Delivery

Biomacromolecules
Daehwan ParkJin Woong Kim

Abstract

We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored coassembly of amphiphilic poly(ethylene oxide)- block-poly(ε-caprolactone) (PEO- b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration was responsible for the deformable phase property of the vehicles. We also discovered that the nanovehicles were mutually attracted, exhibiting a gel-like fluid characteristic due to the dipole-dipole interaction between the hydroxyl group of MEL and the methoxy group of PEO- b-PCL. Coassembly of TAT-linked MEL with the deformable nanovehicles significantly enhanced cellular uptake due to macropinocytosis and caveolae-/lipid raft-mediated endocytosis. Furthermore, the in vivo skin penetration test revealed that our TAT-patchy deformable nanovehicles remarkably improved transdermal delivery efficiency.

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Citations

Dec 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yahua CuiShouying Du
Jun 14, 2020·International Journal of Molecular Sciences·Lamya H Al-WahaibiGamal A Shazly
Jan 26, 2020·Applied Microbiology and Biotechnology·Ana Letícia Silva CoelhoDébora de Oliveira
Dec 9, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jeong Yi KangJin Woong Kim
Jun 11, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jung Hyeon ChoJin Woong Kim

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