4.6 Article

Induction of Spontaneous Liposome Adsorption by Exogenous Surface Modification with Cell-Penetrating Peptide-Conjugated Lipids

Journal

LANGMUIR
Volume 37, Issue 32, Pages 9711-9723

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.1c01072

Keywords

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Funding

  1. Bilateral Joint Research Project (Japan-Sweden) of the Japan Society for the Promotion of Science (JSPS)
  2. STINT
  3. Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan [26702017, 15KK0230, 18KK0305, 19K22951]
  4. Swedish Research Council [2018-04199, 2016-04519, 2016-20755.1]
  5. StemTherapy
  6. Eurostars-2 joint program [E! 113670]
  7. European Union Horizon 2020 research and innovation program
  8. BPIfrance
  9. German Federal Ministry of Education and Research
  10. VINNOVA
  11. RVO
  12. Swedish Research Council [2018-04199] Funding Source: Swedish Research Council
  13. Grants-in-Aid for Scientific Research [19K22951, 18KK0305, 15KK0230] Funding Source: KAKEN

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The study characterized Tat peptide-conjugated PEG-lipids for surface modification of liposomes, showing that the number of incorporated Tat-PEG-lipid moieties strongly influenced the amount of adsorbed liposomes. Additionally, the introduction of a collagenase-cleavable amino acid sequence allowed for efficient harvesting of adsorbed liposomes from the substrate. Overall, Tat-PEG-lipid was found to be a suitable tool for manipulation of liposomes and cells.
The use of amphiphilic molecules such as poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) enables incorporation into liposome surfaces by exogenous addition as a result of the self-assembly with lipids. This technique can be applicable for manipulation of both liposomes and cells. In this study, we aimed to characterize Tat peptide (YGRKKRRQRRR)-conjugated PEG-lipids when used to exogenously surface modify liposomes (size: ca. 100 nm). We earlier reported that cells, which were surface modified with Tat peptides conjugated to PEG-lipids could attach spontaneously to material surfaces without any chemical modification. Here, we synthesized different types of Tat-PEG-lipids by combining PEG of different molecular weights (5 and 40 kDa) with different lipids with three acyl chains (myristoyl, palmitoyl, and stearoyl, respectively) and then studied the spontaneous adsorption of modified liposomes onto a substrate surface induced by the different Tat-PEG-lipids. The amount of adsorbed liposomes strongly depended on the number of incorporated Tat-PEG-lipid moieties: a decrease in both the PEG and the acyl chain lengths led to adsorption of higher amounts of liposomes. Furthermore, when a collagenase-cleavable amino acid sequence was inserted between the Tat sequence and the PEG segment, adsorbed liposomes could be harvested from the substrate by collagenase treatment with no difference in desorption efficiency between the different Tat-PEG-lipids. Thus, Tat-PEG-lipid can be a suitable tool for the manipulation of liposomes and cells.

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