Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles.

Italo Moglia,Simon Guerrero,Margarita Santiago,Marcelo J Kogan,Alvaro Olivera-Nappa,Mónica Soler

doi:10.3390/pharmaceutics13111966

Italo Moglia, Simon Guerrero + Show 4 more

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https://doi.org/10.3390/pharmaceutics13111966

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Abstract

Gold nanoparticles (AuNP) capped with biocompatible layers have functional optical, chemical, and biological properties as theranostic agents in biomedicine. The ferritin protein containing in situ synthesized AuNPs has been successfully used as an effective and completely biocompatible nanocarrier for AuNPs in human cell lines and animal experiments in vivo. Ferritin can be uptaken by different cell types through receptor-mediated endocytosis. Despite these advantages, few efforts have been made to evaluate the toxicity and cellular internalization of AuNP-containing ferritin nanocages. In this work, we study the potential of human heavy-chain (H) and light-chain (L) ferritin homopolymers as nanoreactors to synthesize AuNPs and their cytotoxicity and cellular uptake in different cell lines. The results show very low toxicity of ferritin-encapsulated AuNPs on different human cell lines and demonstrate that efficient cellular ferritin uptake depends on the specific H or L protein chains forming the ferritin protein cage and the presence or absence of metallic cargo. Cargo-devoid apoferritin is poorly internalized in all cell lines, and the highest ferritin uptake was achieved with AuNP-loaded H-ferritin homopolymers in transferrin-receptor-rich cell lines, showing more than seven times more uptake than apoferritin.

Highlights

Gold nanoparticles (AuNP) have great potential as theranostic agents in biomedicine due to their optical, chemical, and biological properties, such as surface plasmon resonance, low chemical reactivity, and reduced cell toxicity
Recombinant human H-ferritin homopolymer (FTH) and L-ferritin homopolymer (FTL) were used as nanocontainers for the synthesis of AuNPs to obtain FTH-AuNP and FTL-AuNP, respectively, following a protocol with two successive gold addition–reduction steps based in a previous protocol published by Fan 2010 [15] (Figure 1)
H-chains mainly internalized by transferrin receptor 1 (TR1), is ubiquitously demonstrate that can be synthesized in both, but nanoparticle synthesis expressed and overexpressed in cancerous and vascular endothelial cell lines [64]. in the gives slightly biggerare nanoparticles andtheis SCARA5 more efficient

Summary

Introduction

Gold nanoparticles (AuNP) have great potential as theranostic agents in biomedicine due to their optical, chemical, and biological properties, such as surface plasmon resonance, low chemical reactivity, and reduced cell toxicity. The use of AuNP for cell targeting requires a protective layer that provides biocompatibility and prevents nonspecific adsorption of proteins as protein coronae, which could impart new biological properties impacting nanoparticle reactivity, bioavailability, and pharmacokinetics, and lead to cytotoxicity or immunotoxicity [1]. The protective biocompatible layer must improve circulating half-life and minimize the reticuloendothelial system uptake that rapidly removes nanoparticles from the circulatory system to the liver, spleen, or bone marrow [2]. Different molecules have been evaluated as protective layers or coating agents for. Polymers such as polyethylene glycol [3], biomolecules such as cysteine [4,5], peptides such as glutathione [6,7], and synthetic peptides [8] and proteins such as bovine serum albumin (BSA) [9–13] and ferritin [14–18] have been used in different biomedical applications.

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