Transport of trans-activator of transcription (TAT) peptide in tumour tissue model: evaluation of factors affecting the transport of TAT evidenced by flow cytometry

Abstract

Objectives Trans‐activator of transcription (TAT), a cell penetrating peptide, has been explored to overcome resistance to penetration and transport inside the cell, therefore, suggested to be used as drug delivery vector into drug‐resistant tumours. The generosity of this study was to evaluate modifiable factors (concentration, temperature, incubation time and spheroid age) on the penetration of TAT. Methods Multicellular tumour spheroids (MCTS) used as tumour tissue models to mimic some characteristics with in‐vivo tumors. Cell monolayer and 3‐, 5‐, 7‐day‐old MCTS were incubated with TAT and effects of modifiable factors were determined quantitatively through flow cytometry, based on TAT‐positive cell count (%) and mean fluorescence intensity. Key findings Enhancing TAT concentration (1, 5 and 25 µm), transport significantly increased (ANOVA, P < 0.0001) in cell monolayer and spheroids. However, rising temperature from 7 to 37°C (t, P > 0.05) and increasing incubation time; 20 min, 1 h and 3 h; (ANOVA, P > 0.05) were statistically non‐significant. Moreover, TAT penetration declines as spheroids get older (ANOVA, P < 0.01). Conclusion While exploiting MCTS as tumour tissue model, older spheroids could be preferred to target penetration‐resistant cells and mimic the in‐vivo microenvironment.

A brain glioma gene delivery strategy by angiopep-2 and TAT-modified magnetic lipid-polymer hybrid nanoparticles

“…[17][18][19] CPPs can penetrate the plasma membrane and the nucleus of almost any live cells. 20,21 As a kind of CPP, the transactivator of transcription (TAT) peptide has shown fast endosomal or lysosomal escape and quick nuclear localization, and can easily penetrate through biolm barriers like the BBB. 22,23 TAT and Ang can bind to DSPE-PEG 2000 -MAL with the cysteine structure through the MAL molecule group.…”

Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

“…As a commonly used CPP, trans-Activator of Transcription (TAT) protein was recently evaluated on solid tumors using the multicellular tumor spheroids as cell models. It showed that higher TAT concentrations significantly increased peptide uptake ( 51 ). In addition to TAT, penetratin, GALA, transportan, and its derivatives such as PepFect and NickFect have also received attention for their cell penetration abilities ( 52 ).…”

Nanotechnology Advances in the Detection and Treatment of Cancer: An Overview

“…Some researchers are therefore designing techniques whereby the whole drug-nanoparticle structure may penetrate cancer cells before the actual release of pharmacological drugs into the cytosol to improve the accuracy of drug distribution to appropriate intracellular targets 108 , 109 . They are working to promote intracellular absorption by marking nanomaterials with peptides to penetrate the cells, like Penetration and anti-actin-targeting substances such as transcription transactivator (TAT) peptide in accompanying with a nice arrow peptide 110 , 111 . As most of the mentioned compounds have main objectives inside the cells, they are anticipated to have a stronger therapeutic impact.…”