Cell penetrating peptide Liposomes

Figure 2 Proposed pathways for liposomal entry into the cell enhanced by peptides. These include direct cell entry suggested as the mechanism of entry by cell-penetrating peptides and receptor-mediated endocytosis by caveolae- and clathrin-dependent endocytosis.

Marty C, Meylan C, Schott H, et al. Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes. Cell Mol Life Sci 2004 61 (14) 1785-1794. 

Already in 1965, Ryser and Hancock provided evidence that histones and polyamino acids could greatly enhance albumin uptake by cultured tumor cells (6). More recently, several polybasic peptides (so-called protein transduction domains, PTDs or cell-penetrating peptides, CPPs) have been shown to efficiently mediate uptake of nucleic acids, bioactive peptides, phage particles, and liposomes into a wide variety of mammalian cells. The initially proposed ability of CPPs to penetrate plasma membranes via a temperature-independent, non-endocytotic pathway was later shown to be a fixation artifact, and it is currently widely accepted that CPP-mediated macromolecular delivery follows energy-dependent endocytotic pathways that in most cases depend on the expression of cell-surface heparan sulfate proteoglycans (HSPGs) (7). 

Tseng, Y. L., Liu, J. J., and Hong, R. L. (2002) Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat a kinetic and efficacy study. Mol. Pharmacol. 62, 864-872. 

Key words pH-sensitive liposomes, Cell penetrating peptide, TATp, Hydrazone, PEG-PE, Enhanced permeability and retention... 

Jiang T, Zhang Z, Zhang Y, Lv H, Zhou J, Li C et al. Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery. Biomaterials. 2012 33(36) 9246-9258. 

For DNA and RNA delivery to the central nervous system (CNS), numerous nonviral nanosystems can be employed [10], These include cationic and stealth liposomes, cationic polymers, dendrimers, cyclodextrin, and cell-penetrating peptides (CPPs). In general terms, all these synthetic vectors lack of a cytotropism, i.e., they do not specifically target a single type/subtype of cell, and display different degrees of cytotoxicity. 

Nonviral synthetic vectors (cationic liposomes/polymers, dendrimers, cyclodextrin, ceU-penetrating peptides) Vector can cross cell membrane Easy to handle Technically simple Low transfection efficiency and toxicity in certain cases Yes It is possible to perform site directed injections (microinjections)... 

---