Peptide-mediated protein delivery-which pathways are penetrable?

Area of Science:

• Biotechnology and Nanomedicine
• Molecular and Cellular Biology

Background:

• Cell-penetrating peptides (CPPs) are increasingly recognized for their potential in delivering various cargoes into cells.
• However, the precise mechanisms of CPP-cargo complex internalization and subsequent intracellular trafficking are not well understood, with conflicting data reported.
• Limited knowledge exists regarding the fate of CPP-cargo complexes within the cellular environment.

Purpose of the Study:

• To critically review and define the endocytic pathways involved in the cellular uptake of CPP-cargo complexes.
• To elucidate the extent to which different endocytic routes contribute to the effective transduction of CPP-cargo complexes.
• To discuss the intracellular trafficking, sorting, and ultimate fate of CPP-cargo complexes within cells.

Main Methods:

• This review synthesizes existing literature on CPP-mediated delivery.
• It analyzes data on CPP-cargo complex internalization mechanisms, focusing on endocytic pathways.
• The review also examines studies investigating intracellular trafficking and the fate of these complexes.

Main Results:

• Data on CPP-cargo complex internalization modes are often conflicting and equivocal.
• The intracellular trafficking and sorting of CPP-cargo complexes are relatively unexplored areas.
• Minimal information is available on the ultimate fate of CPP-cargo complexes after cellular entry.

Conclusions:

• A clearer understanding of CPP-cargo complex endocytosis is crucial for optimizing their delivery efficiency.
• Further research into the intracellular trafficking and fate of CPP-cargo complexes is needed.
• Elucidating these processes will enhance the development of CPP-based therapeutic strategies.