Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Abstract

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

New Advances in Biomedical Application of Polymeric Micelles

“…Programmed drug release from Pluronic micelles has also been exploiting stimuli-sensitive linkers that are sensitive to extra-and intra-cellular cues such as pH, redox system, or enzymes. Non-specific electrostatic interactions of Pluronic micelles that were grafted with cationic polymers such as polyethyleneimine with negatively charged cell and organelle membranes can also be exploited to increase cellular uptake but also to deliver negatively charged therapeutics such as nucleic acids, which opened up wide application of Pluronic micelles in combination with drug-gene therapy [115][116][117]. The ability of Pluronic ® micelles to be taken up by various immune cells such as myeloid-derived suppressor cells or dendritic cells is increasingly employed in the design of new immunocancer therapies [118,119].…”

Fusogenic peptide modification to enhance gene delivery by peptide-DNA nano-coassemblies

“…This capability can be attributed to the presence on the virus capsid fusogenic proteins specialized for endosomal escape. 5 A number of fusogenic peptides of both viral and non-viral origin, such as HA2, 11 INF7, 12 RALA/GALA families 13 and L17E/HAad families, 14 have been confirmed for their ability to disrupt endosomal membrane and increase cytosol delivery. 15 Incorporation of HA2 on the non-viral gene carriers, such as organosilica NPs 16 and HPMA co-polymer, 17 enhanced the transfection efficiency.…”

A self-assembling peptidic platform to boost the cellular uptake and nuclear delivery of oligonucleotides

“…19 An efficient alternative to overcome these limitations would be the design of highly ordered peptide nanoassemblies because limitless combinations of amino acid sequences and diverse secondary structures offer many options for enhancing cellular internalization and targeting delivery. [20][21][22] However, to make the peptide prone to self-assembly requires the rational selection of its amino acid building blocks and the precise understanding of their chemical properties that determine the interactions between peptides.…”