Multifunctional Gold Nanoparticle−Peptide Complexes for Nuclear Targeting

Abstract

The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

“…For example, charged particles (such as cationic quantum dots or dendrimers, mostly assisted by some degree of hydrophobicity) induce transient poration of cell membranes to enter cells, a process associated with cytotoxicity 18 . Alternatively, nanoparticles have been designed to explicitly disrupt endolysosomal membranes to enter the cell by force 19 or enter the cell aided by exogenous agents such as CPP chaperones 20 . In contrast, most nanoparticles are trapped in endosomes 21 and hence do not reach the cytosol.…”

Ipomea carnea-based silver nanoparticle synthesis for antibacterial activity against selected human pathogens

“…Nanoparticles are being studied for many applications, including biosensors, labels for cells and biomolecules, anti-microbial agents and cancer therapeutics [1][2][3][4]. Silver nanoparticles have wide industrial applications in electrocatalysis, chemical sensors, catalysis and optical devices [5][6][7][8].…”

Monodisperse Magnetite Nanoparticles Coupled with Nuclear Localization Signal Peptide for Cell‐Nucleus Targeting

“…It is known to act as a 'vector' to direct the protein into the cell nucleus through the nuclear pore complex, [17,18] and was recently applied to Au-and dextran-coated iron oxide nanoparticles for their targeting to cell nuclei. [19][20][21][22] Different from these previous functionalization steps, our approach is to conjugate biotinylated NLS to monodisperse Fe 3 O 4 nanoparticles through NeutrAvidin (NAv) and a surfactant combination of polyethylene glycol (PEG) and dopamine (DPA), or 4-(2-aminoethyl)benzene-1,2-diol. DPA can form a strong chelate chemical bond with the iron oxide surface, [23,24] and PEG has been used widely to protect nanoparticles for their stabilization under physiological conditions.…”