PCI as a delivery platform

Stock DZ
11.07.2018 kl 20:56
3098

Dette er en arkivert tråd!
Snøffelen/FiloD/ILAV (or anyone with medical expertise)

I hope you can look into this and let us know what you think as I am not an expert in cell biology.

This is a recently published article (11/07/2018) titled:
"Efficient Delivery of Macromolecules into Human Cells by Improving the Endosomal Escape Activity of Cell-Penetrating Peptides: Lessons Learned from dfTAT and its Analogs"

it is stating what could be a challenge with PCI technology!!.

Link
www.mdpi.com/2218-273X/8/3/50/pdf

in particular it reads:

***Page-2:
"Another approach that we investigated was that of photochemical internalization, which is a strategy that relies on the photooxidation of endosomal membranes [12–14]. In particular, similar to other groups, we used fluorescently-labeled CPPs to induce endosomal escape by irradiation with visible light [15,16]. Although very rapid and efficient, we found that this light-induced endosomal escape is accompanied by a rapid burst of calcium release into the cell. This, in turn, leads to mitochondrial permeabilization and cell death, which is an obvious problem [16]."

**Page 10/11
"Efficient cell penetration by macromolecules requires the permeation of cellular membranes. In principle, it is often thought that the higher the efficiency of the cell penetration event, the more damaging the process is to membranes, and therefore, to the cell [39,40]. In other words, how does one let large molecules enter a cell without creating large holes in cellular barriers and without destroying these barriers?"

"As highlighted in our introduction, this is the case with CPP-mediated photochemical internalization (PCI), which is a process that leads to the rapid and toxic burst of calcium release from the lumen of endosomes to the cytosol and mitochondria of cells. In principle, calcium is also released from late endosomes, which are permeabilized by dfTAT. However, dfTAT-mediated cell penetration is a process that takes place on a scale of minutes, not seconds, as with PCI. Therefore, we envision that the leakage of calcium into cells during dfTAT treatment may be relatively slow and progressive, leaving cells time to re-establish homeostasis. Overall, regardless of why their permeation is tolerated, late endosomes appear to be a desirable and exploitable gateway into cells"

I hope to get your opinions on this!

Redigert 11.07.2018 kl 21:01 Arkivert