Abstract
Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery.
Highlights
When when connecting toother otherpeptides, peptides, assembly may be influenced by other amino connecting ititto thethe assembly may be influenced by other amino acids,acids, such such as Arg, Pro,[15]
We report a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)
Measured by gel retardation assays and UV, we confirmed that 1mg peptide can load
Summary
Nonviral systems have gained wide attention because of the activation of oncogenes and excessive immunogenicity of viral vectors [1]. To absorb genes first and penetrate the cell membrane, cationic polymers such as polyethyleneimine (PEI) [2,3,4,5] and poly-(L-lysine) (PLL) [6] have been proposed. Significant toxicity can be observed in cells or animals after the administration of PEI. PEI was reported to activate Fasl-mediated antigen-induced cell death in the spleen [7]. Systemic administration of PEI caused liver necrosis and death, as well as the increase of small aggregates of both platelets and CD11-b-positive cells in the lung [8]. PLL shows its very toxicity, which increases with the increment of its molecular weight [9].
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