Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery

Abstract

The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanoparticles based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified nanoparticles was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanoparticles with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized HSA nanoparticles represent promising tools for efficient and safe gene therapy.

Protein based therapeutic delivery agents: Contemporary developments and challenges

“…Unmodified albumin mostly fails to bind nucleic acid materials and to penetrate cell and nuclear membranes [206]. Cationization of albumins is a common strategy to improve the transfection; however, the efficiency may still be limited [193]. In a study using cationic bovine serum albumin (CBSA) as the gene carrier, B-cell lymphoma 2 (Bcl2) specific siRNA exhibits decent antitumor activity in a B16 lung metastasis model when delivered by CBSA [192].…”

Gene-silencing effects of anti-survivin siRNA delivered by RGDV-functionalized nanodiamond carrier in the breast carcinoma cell line MCF-7

“…The sediment was freeze dried, and carboxylated ND was obtained. 20,24,25 synthesis of NDcONh(ch 2 ) 2 Nh 2 Carboxylated ND (200 mg) was added to 10 mL of thionyl chloride, the reaction was carried out at 70°C for 12 h, and NDCOCl was obtained ( Figure 1, step ii). NH 2 CH 2 CH 2 NHBoc (50 mg) and tetrahydrofuran were then added, and the suspension was stirred at 60°C for 6 h. After the reaction, the mixture was centrifuged at 5,000 g for 15 min and washed three times with distilled water.…”

“…23 However, synthesizing a highefficient targeting carrier using ND is still a challenge. 24 RGD peptides, ligands for α v β 3 -intergrin, are known as an effective tool for targeting tumor cells. [25][26][27] In this study, we prepared a novel targeted gene delivery system, NDCONH(CH 2 ) 2 NH-VDGR, containing ND (gene delivery vehicle), H-Arg-GlyAsp-Val-OH (targeting agent), and EDA (joint arm), and the targeting and transfection efficiency was studied.…”

Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

“…Moreover, the presence of functional carboxylic and amino groups on the surface facilitates the surface functionalization for albumin nanoparticles [19, 20]. For example, via covalent binding, the surface of albumin nanoparticles can be decorated with fluorescence dyes, target molecules, and functional RNA [21, 22]. Also, it can be readily functionalized with hydrophilic polymers, such as PEG, to prolong the blood circulation [23].…”