Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution

Rossi, Luigia; Pierigé, Francesca; Antonelli, A.; Bigini, Noemi; Gabucci, Claudia; Peiretti, Enrico; Magnani, Mauro

doi:10.1016/j.addr.2016.05.008

Cited by 49 publications

(32 citation statements)

References 155 publications

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“…These achievements (summarized in the next sections) are possible only thanks to the exclusive features of these cells which allow them to be engineered without altering their properties or compromising their in vivo circulation. In fact, the biochemical characteristics of RBC, their physiology as well as the molecular mechanisms governing the natural fate of the senescent or damaged cells, make them attractive candidates as carriers of conventional and/or new drugs, as extensively documented in recent, excellent, reviews . RBC are among the most abundant cell types in a human body: they comprise approximately one quarter of the total cell number and are the main component of blood with the crucial role of carriers of oxygen and carbon dioxide.…”

Section: Biology and Circulation Of Human Rbcmentioning

confidence: 99%

Reengineering red blood cells for cellular therapeutics and diagnostics

Pierigé

Bigini

Rossi

et al. 2017

WIREs Nanomed Nanobiotechnol

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Recently optimized technologies that permit the reversible opening of nanopores across the red blood cell membrane, give the extraordinary opportunity for reengineering human erythrocytes to be used in different biomedical applications, both for therapeutic and diagnostic purposes. Engineered erythrocytes have been exploited as a system for the controlled release of drugs in circulation upon encapsulation of prodrugs or small molecules; as bioreactors when they are endowed of recombinant enzymes able to catalyze the conversion of toxic metabolite into inert products; as drug targeting system for the delivery of compounds to the reticuloendothelial system inducing proper senescent signals on the drug-loaded erythrocyte membrane; as carrier of contrasting agents for diagnostic procedures. Preclinical development of these different applications has taken advantage from the use of proper animal models whose erythrocytes can be reengineered as the human ones or the encapsulation procedures can be adapted on the basis of their specific erythrocyte biological features. Successful results, obtained both in vitro and in preclinical studies, have prompted several clinicians to start pilot clinical investigations in different conditions and some new companies to start the industrialization of selected loading technologies and to initiate clinical development programs. This short review summarizes the key features that, to the best of our knowledge, have been crucial to advance the products toward regulatory clinical approval making reengineering of erythrocytes a modality to treat patients with limited or absent therapeutic options. WIREs Nanomed Nanobiotechnol 2017, 9:e1454. doi: 10.1002/wnan.1454 For further resources related to this article, please visit the WIREs website.

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Section: Biology and Circulation Of Human Rbcmentioning

confidence: 99%

Reengineering red blood cells for cellular therapeutics and diagnostics

Pierigé

Bigini

Rossi

et al. 2017

WIREs Nanomed Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

show abstract

“…According to data regarding cell-based therapies, those using erythrocytes have proved to be the most stable, versatile, safe, and easy to manufacture. This strategy is based on temporarily opening pores in the membrane of erythrocytes, easily transporting drugs and ensuring that the latter can stay within these cells once the pores have closed [33]. One of the main uses for this system is the delivery of contrast agents contained within superparamagnetic iron oxide (SPIO) nanoparticles, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, very small superparamagnetic iron oxide (VSPIO) nanoparticles, and monocrystalline iron oxide nanocompound (MION) particles, which are already registered and approved for use in the United States and Europe [34].…”

Section: Interaction Of Nanomaterials With Red Cellsmentioning

confidence: 99%

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Cruz¹,

Rodríguez-Fragoso²,

JorgeReyes-Esparza³

et al. 2018

Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications

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Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials' first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood's components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary.

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“…Efforts have been directed to (1) directly encapsulate therapeutics inside RBC; (2) piggyback nanoparticles on their membrane; and (3) create RBC membrane cloaked polymeric drug delivery vehicles. Various methods such as hypotonic haemolysis, electroinsertion, or endocytosis have been developed to encapsulate pharmacological and imaging agents, including enzymes, peptides, small molecules drugs, fluorescent labels, and oligonucleotides, into RBC without a secondary synthetic nanoparticle . Several of these formulations are now in clinical trials .…”

Section: Cell‐based Biohybrid Drug Delivery Systemmentioning

confidence: 99%

“…Various methods such as hypotonic haemolysis, electroinsertion, or endocytosis have been developed to encapsulate pharmacological and imaging agents, including enzymes, peptides, small molecules drugs, fluorescent labels, and oligonucleotides, into RBC without a secondary synthetic nanoparticle . Several of these formulations are now in clinical trials . However, direct encapsulation of therapeutics is out of the scope of this review, and has been extensively reviewed elsewhere .…”

Section: Cell‐based Biohybrid Drug Delivery Systemmentioning

confidence: 99%

Cell‐Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds

Banskota

Yousefpour

Chilkoti

2016

Macromolecular Bioscience

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The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles. Examples include eukaryotic cells, such as stem cells, red blood cells, immune cells, platelets, and cancer cells that are used to carry drug-loaded synthetic particles. Synthetic particles can also be cloaked with naturally derived cell membranes and thereby evade immune clearance, exhibit prolonged systemic circulation, and target specific tissues by capitalizing on the interaction/homing tendency of certain cells and their membrane components to particular tissues. Different designs of cell-based biohybrid systems and their applications, as well as their promise and limitations, are discussed herein.

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Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution

Cited by 49 publications

References 155 publications

Reengineering red blood cells for cellular therapeutics and diagnostics

Reengineering red blood cells for cellular therapeutics and diagnostics

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Cell‐Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds

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