Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Abstract

Gene therapy offers the possibility to skip, repair, or silence faulty genes or to stimulate the immune system to fight against disease by delivering therapeutic nucleic acids (NAs) to a patient. Compared to other drugs or protein treatments, NA-based therapies have the advantage of being a more universal approach to designing therapies because of the versatility of NA design. NAs (siRNA, pDNA, or mRNA) have great potential for therapeutic applications for an immense number of indications. However, the delivery of these exogenous NAs is still challenging and requires a specific delivery system. In this context, beside other non-viral vectors, cell-penetrating peptides (CPPs) gain more and more interest as delivery systems by forming a variety of nanocomplexes depending on the formulation conditions and the properties of the used CPPs/NAs. In this review, we attempt to cover the most important biophysical and biological aspects of non-viral peptide-based nanoparticles (PBNs) for therapeutic nucleic acid formulations as a delivery system. The most relevant peptides or peptide families forming PBNs in the presence of NAs described since 2015 will be presented. All these PBNs able to deliver NAs in vitro and in vivo have common features, which are characterized by defined formulation conditions in order to obtain PBNs from 60 nm to 150 nm with a homogeneous dispersity (PdI lower than 0.3) and a positive charge between +10 mV and +40 mV.

Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

“…Therapies based on nucleic acids are versatile because of their design, which offers promising treatments. Nevertheless, a particular delivery system is required for their delivery [54].…”

“…Moreover, because of their low toxicity and facilitated cellular uptake, multifunctional protein-based nanocarriers hold great promise for the delivery of nucleic acids, such as DNA, short-interfering RNA (siRNA), etc. [53,54]. Through this review, we hoped to cast light on the nanotechnology-based techniques for sensing AAs/peptides/proteins and provide new insights into exploiting protein-based nanoassemblies for targeted delivery of specific drugs or genes.…”

Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions

“…This nanoconjugate showed 19-fold more tumor accumulation and 46-fold cellular uptake compared to the commercial siRNA nanocarrier jetPEI, in a mouse orthotopic model of human triple-negative breast cancer [ 74 ]. Despite the various advantages of modifying the nucleic acids to increase the stability, pharmacokinetics and pharmacodynamic properties, and enhancement of internalization and endosomal escape, limited work has been done using albumin nanocarriers [ 75 ]. Further studies integrating the advantages of albumin nanocarriers with the modified nucleic acids can be of great potential in cancer therapy.…”

The Potential of Cell-Penetrating Peptides for mRNA Delivery to Cancer Cells

“…New mRNA delivery systems should meet simple production and improved biocompatibility. In terms of high transfection efficiency, safety and low production cost, peptide-based delivery offers great promise [23]. Cell-penetrating peptides (CPPs) are usually 4-40 amino acids long and possess cationic or amphipathic motifs that have the ability to cross the cell membrane [24].…”