A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

Zhang, Quan; Zhang, Xuanmiao; Chen, Tijia; Wang, Xinyi; Fu, Yao; Jin, Yun; Sun, Xun; Gong, Tao; Zhang, Zhirong

doi:10.1039/c4nr04730c

Cited by 16 publications

(9 citation statements)

References 77 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, PEG-capped NPs have been used in medical applications, which has been proposed to allow for the targeted delivery of drugs. 13 Although it is known that the alteration of the capping agent can dramatically affect the nanoparticlesize, shape, and interaction with the solvent effects of the capping agent on microscopic solution dynamics are still rarely understood. Electrochemical analysis has been shown to provide insight into the properties of individual nanoparticles, allowing the sizing of individual particles, 14 the estimation of aggregation 15 and electrostatic effects, 16 and the measurement of concentrations of NPs in various complex media.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Citrate-capped NPs are frequently used for a variety of applications, while PEG modification is particularly valued in contexts with high ionic strength. Specifically, PEG-capped NPs have been used in medical applications, which has been proposed to allow for the targeted delivery of drugs . Although it is known that the alteration of the capping agent can dramatically affect the nanoparticlesize, shape, and interaction with the solventeffects of the capping agent on microscopic solution dynamics are still rarely understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nanoparticle Capping Agent Dynamics and Electron Transfer: Polymer-Gated Oxidation of Silver Nanoparticles

et al. 2015

View full text Add to dashboard Cite

Capping agent-controlled stability of nanoparticles tailors them for different applications, but the associated particle−solvent dynamics are poorly understood. Herein, previously unseen capping agent-gated nanoparticle redox activity is observed for poly(ethylene glycol)-coated silver nanoparticles. This is revealed by stochastic nanoparticle stripping, probing one individual nanoparticle at a time, from an ensemble of surface-immobilized nanoparticles. Thus, new and previously inaccessible understanding is gained on the crucial role of capping agent dynamics on nanoparticle reactivity.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoparticle Capping Agent Dynamics and Electron Transfer: Polymer-Gated Oxidation of Silver Nanoparticles

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Indeed, various hepatic drug delivery platforms using MyrB or its derivatives have been proposed as targeting ligands. − These efforts have focused primarily on liposome-based strategies, demonstrating effective delivery of small molecule drugs such as paclitaxel or doxorubicin . Similarly, we optimized virus-mimetic lipid nanocarriers coupled to a MyrB derivative .…”

Section: Introductionmentioning

confidence: 99%

Virus-Derived Peptides for Hepatic Enzyme Delivery

et al. 2021

View full text Add to dashboard Cite

Recently, a lipopeptide derived from the hepatitis B virus (HBV) large surface protein has been developed as an HBV entry inhibitor. This lipopeptide, called MyrcludexB (MyrB), selectively binds to the sodium taurocholate cotransporting polypeptide (NTCP) on the basolateral membrane of hepatocytes. Here, the feasibility of coupling therapeutic enzymes to MyrB was investigated for the development of enzyme delivery strategies. Hepatotropic targeting shall enable enzyme prodrug therapies and detoxification procedures. Here, horseradish peroxidase (HRP) was conjugated to MyrB via maleimide chemistry, and coupling was validated by SDS-PAGE and reversed-phase HPLC. The specificity of the target recognition of HRP-MyrB could be shown in an NTCP-overexpressing liver parenchymal cell line, as demonstrated by competitive inhibition with an excess of free MyrB and displayed a strong linear dependency on the applied HRP-MyrB concentration. In vivo studies in zebrafish embryos revealed a dominating interaction of HRP-MyrB with scavenger endothelial cells vs xenografted NTCP expressing mammalian cells. In mice, radiolabeled 125I-HRP-MyrBy, as well as the non-NTCP targeted control HRP-peptide-construct (125I-HRP-alaMyrBy) demonstrated a strong liver accumulation confirming the nonspecific interaction with scavenger cells. Still, MyrB conjugation to HRP resulted in an increased and NTCP-mediated hepatotropism, as revealed by competitive inhibition. In conclusion, the model enzyme HRP was successfully conjugated to MyrB to achieve NTCP-specific targeting in vitro with the potential for ex vivo diagnostic applications. In vivo, target specificity was reduced by non-NTCP-mediated interactions. Nonetheless, tissue distribution experiments in zebrafish embryos provide mechanistic insight into underlying scavenging processes indicating partial involvement of stabilin receptors.

show abstract

“…Based on these findings, the question arises whether Myrcludex B might serve as a targeting ligand to design a hepatotropic, NTCP-specific nanoparticle. In recent years, several groups have therefore attempted to develop targeting strategies based on HBV envelope proteins, for example recombinant HBV envelope protein particles (bio-nanocapsules) or HBV preS1-derived functionalized liposomes (Liu et al, 2016; Somiya et al, 2016; Somiya et al, 2015; Zhang et al, 2015; Zhang et al, 2014). However, the nanoparticulate drug delivery systems developed had physicochemical properties (e.g.…”

Section: Introductionmentioning

confidence: 99%

Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide

Witzigmann

Uhl

Sieber

et al. 2019

eLife

View full text Add to dashboard Cite

Active targeting and specific drug delivery to parenchymal liver cells is a promising strategy to treat various liver disorders. Here, we modified synthetic lipid-based nanoparticles with targeting peptides derived from the hepatitis B virus large envelope protein (HBVpreS) to specifically target the sodium-taurocholate cotransporting polypeptide (NTCP; SLC10A1) on the sinusoidal membrane of hepatocytes. Physicochemical properties of targeted nanoparticles were optimized and NTCP-specific, ligand-dependent binding and internalization was confirmed in vitro. The pharmacokinetics and targeting capacity of selected lead formulations was investigated in vivo using the emerging zebrafish screening model. Liposomal nanoparticles modified with 0.25 mol% of a short myristoylated HBV derived peptide, that is Myr-HBVpreS2-31, showed an optimal balance between systemic circulation, avoidance of blood clearance, and targeting capacity. Pronounced liver enrichment, active NTCP-mediated targeting of hepatocytes and efficient cellular internalization were confirmed in mice by 111In gamma scintigraphy and fluorescence microscopy demonstrating the potential use of our hepatotropic, ligand-modified nanoparticles.

show abstract

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

Cited by 16 publications

References 77 publications

Nanoparticle Capping Agent Dynamics and Electron Transfer: Polymer-Gated Oxidation of Silver Nanoparticles

Nanoparticle Capping Agent Dynamics and Electron Transfer: Polymer-Gated Oxidation of Silver Nanoparticles

Virus-Derived Peptides for Hepatic Enzyme Delivery

Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide

Contact Info

Product

Resources

About