Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways

Toy, Randall; Pradhan, Pallab; Ramesh, Vijayeetha; Paolo, Nelson C. Di; Lash, Blake; Liu, Jiaying; Blanchard, Emmeline L.; Pinelli, Christopher; Santangelo, Philip J.; Shayakhmetov, Dmitry M.; Roy, Krishnendu

doi:10.1016/j.biomaterials.2019.119512

Cited by 23 publications

(26 citation statements)

References 49 publications

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“…Magnetic nanoparticle (MNP)-infiltrated bone regeneration scaffolds could also adsorb inflammatory related protein such as alpha-2-HSglycoprotein, haptoglobin, and complement components, which can activate the immune system (Figure 2A; Zhu et al, 2019). In addition, Toy et al (2019) found that imidazole-aceticacid (IAA) modification polyethyleneimine (bPEI) NPs adsorbed less fibrinogen than bPEI NPs, and thus have reduced immune activation and expression of chemokine expression. Moreover, blood hemolysis, liver toxicity, and anaphylactic responses were also reduced.…”

Section: Toxicity To Immune Systems and Othersmentioning

confidence: 99%

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Bai

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs’ safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.

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Section: Toxicity To Immune Systems and Othersmentioning

confidence: 99%

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Bai

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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“…Since toxicity is related in part to the non-biodegradability of these polymers, reducing their molecular weight and degree of branching can decrease their toxicity. Alternatively, modification of these dendrimers with histidines has been shown to mitigate their toxicity [ 55 , 56 , 57 , 67 , 68 ]. By conjugating imidazoles to branched PEI, reduced toxicity of the modified PEI was observed in vivo and was mediated by a decrease of cytokines, chemokines, and reduced liver injury [ 68 ].…”

Section: Beyond H-k Peptides and Polymersmentioning

confidence: 99%

“…Alternatively, modification of these dendrimers with histidines has been shown to mitigate their toxicity [55][56][57]67,68]. By conjugating imidazoles to branched PEI, reduced toxicity of the modified PEI was observed in vivo and was mediated by a decrease of cytokines, chemokines, and reduced liver injury [68].…”

Section: Non-biodegradable Polymersmentioning

confidence: 99%

The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges

Mixson

2020

Pharmaceutics

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Histidines incorporated into carriers of nucleic acids may enhance the extracellular stability of the nanoparticle, yet aid in the intracellular disruption of the nanoparticle, enabling the release of the nucleic acid. Moreover, protonation of histidines in the endosomes may result in endosomal swelling with subsequent lysis. These properties of histidine are based on its five-member imidazole ring in which the two nitrogen atoms may form hydrogen bonds or act as a base in acidic environments. A wide variety of carriers have integrated histidines or histidine-rich domains, which include peptides, polyethylenimine, polysaccharides, platform delivery systems, viral phages, mesoporous silica particles, and liposomes. Histidine-rich carriers have played key roles in our understanding of the stability of nanocarriers and the escape of the nucleic acids from endosomes. These carriers show great promise and offer marked potential in delivering plasmids, siRNA, and mRNA to their intracellular targets.

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“…Multifunctional cationic polymers combining biolm dispersal, bactericidal and anti-persister activity can be designed to be highly effective antibiolm agents, which lls a signicant gap in the current therapeutic armamentarium. Another noteworthy point is that many cationic polymers have exhibited nephrotoxicity and hepatotoxicity in vivo or in clinical studies due to their cationicity, [178][179][180][181] even though they do not show any toxicity in vitro. These in vivo toxicities may be addressable with cationic polymers with "on-demand" antimicrobial ability triggered by bacterial infectious environment.…”

Section: Discussionmentioning

confidence: 99%

Polymers as advanced antibacterial and antibiofilm agents for direct and combination therapies

Wang

Pranantyo

et al. 2022

Chem. Sci.

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Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways

Cited by 23 publications

References 49 publications

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges

Polymers as advanced antibacterial and antibiofilm agents for direct and combination therapies

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