Peptide modified gold nanoparticles for improved cellular uptake, nuclear transport, and intracellular retention

Abstract

Gold nanoparticles (GNPs) are being extensively used in cancer therapeutic applications due to their ability to act both as an anticancer drug carrier in chemotherapy and as a dose enhancer in radiotherapy. The therapeutic response can be further enhanced if nanoparticles (NPs) can be effectively targeted into the nucleus. Here, we present an uptake and removal of GNPs functionalized with three peptides. The first peptide (RGD peptide) enhanced the uptake, the second peptide (NLS peptide) facilitated the nuclear delivery, while the third one (pentapeptide) covered the rest of the surface and protected it from the binding of serum proteins onto the NP surface. The pentapeptide also stabilized the conjugated GNP complex. The peptide-capped GNPs showed a five-fold increase in NP uptake followed by effective nuclear localization. The fraction of NPs exocytosed was less for peptide-capped NPs as compared to citrate-capped ones. Enhanced uptake and prolonged intracellular retention of peptide-capped GNPs could allow NPs to perform their desired applications more efficiently in cells. These studies will provide guidelines for developing NPs for therapeutic applications, which will require "controlling" of the NP accumulation rate while maintaining low toxicity.

Plasmonic labeling of subcellular compartments in cancer cells: multiplexing with fine-tuned gold and silver nanoshells

“…endoplasmic reticulum, Golgi complex). 34 In order to demonstrate the feasibility of using nanoshells as a multiplex platform for cell analysis in both domains (intra and extracellular), the nanoparticle surface was functionalized with either a NLS (nuclear localization signal) peptide or an anti-IGFR antibody. The nanoshells modified with NLS peptides are expected to be internalized and localized to the nuclear membrane.…”

Comparative evaluation of immunohistochemistry and real-time PCR for measuring proinflammatory cytokines gene expression in livers of rats treated with gold nanoparticles

“…Recently we have shown that complement system plays an important role in uptake and clearance of nanoparticles as well as the modulation of proinflammatory immune response (Pondman et al, 2015). Yang et al (2014) functionalized the GNPs with three different peptides including RGD peptide, NLS peptide and pentapeptide. This functionalization enhanced the uptake (RGD peptide), facilitated the nuclear delivery (NLS peptide) and covered the rest of the surface (pentapeptide) resulting in protection of the peptide-capped GNPs from the binding of serum proteins (e.g.…”

Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles

“…The dose enhancement to high-value targets, e.g., the nucleus, is expected to be higher for GNPs closer to the target and lower for GNPs farther away from the target. A recent study [25] shows that nuclear targeting with nanoparticles is achievable and could thus be employed here to maximize damage to the tumor cells DNA.…”