Neutrophil-Mediated Transport is Crucial for Short-Circulating Magnetic Nanoparticles Delivery to Tumors

Naumenko, Victor; Никитин, А. А.; Garanina, Anastasiia S.; Melnikov, Pavel; Vodopyanov, Stepan S.; Kapitanova, Ksenia; Potashnikova, Daria; Vishnevskiy, Daniil A.; Alieva, Irina B.; Ilyasov, Artem; Abakumov, Maxim A.; Чехонин, В. П.; Majouga, Alexander

doi:10.2139/ssrn.3473989

Cited by 2 publications

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“…The entry of nanoparticles to injured tissue has conventionally been considered to occur via the EPR effect. However, recent studies have found that nanoparticles can enter tumors through trans-endothelial pathways or utilize leukocytes, especially neutrophils and macrophages, as mediators for entry [ 196 , 197 , 198 ]. More technologies, e.g., real-time in vivo imaging with high resolution, may be needed to uncover the delivery process for nanoparticles.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Wang

Zhou

et al. 2021

Pharmaceutics

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Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.

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Section: Conclusion and Prospectsmentioning

confidence: 99%

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Wang

Zhou

et al. 2021

Pharmaceutics

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“…While some SPION can induce these immune responses, others exert an inhibitory effect, thereby highlighting composition as a key factor when considering nanoparticle use as a therapeutic ( 2 , 11 ). Conventional wisdom is that nanoparticle clearance is mediated by macrophages; however, recent studies indicate that neutrophils also play a key role in particle clearance and this process has been exploited to deliver therapeutic nanoparticles to tumors for cancer therapy ( 12 , 13 ). Current literature on the immune effects of SPION have largely focused on monocytes and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Inflammatory Response Is Downregulated by Uptake of Superparamagnetic Iron Oxide Nanoparticle Therapeutics

et al. 2020

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Superparamagnetic iron oxide nanoparticles (SPION) are employed as diagnostics and therapeutics following intravenous delivery for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney failure. Neutrophils are the first defense against blood borne foreign insult and recruit to vascular sites of inflammation via a sequential process that is characterized by adhesive capture, rolling, and shear resistant arrest. A primary chemotactic agonist presented on the glycocalyx of inflamed endothelium is IL-8, which upon binding to its cognate membrane receptor (CXCR1/2) activates a suite of responses in neutrophils. An early response is degranulation with accompanying upregulation of β2-integrin (CD11/CD18) and shedding of L-selectin (CD62L) receptors, which exert differential effects on the efficiency of endothelial recruitment. Feraheme is an FDA approved SPION treatment for IDA, but its effect on the innate immune response of neutrophils during inflammation has not been reported. Here, we studied the immunomodulatory effects of Feraheme on neutrophils freshly isolated from healthy human subjects and stimulated in suspension or on inflammatory mimetic substrates with IL-8. Cells treated with Feraheme exhibited reduced sensitivity to stimulation with IL-8, indicated by reduced upregulation of membrane CD11b/CD18 receptors, high affinity (HA) CD18, and shedding of CD62L. Feraheme also inhibited N-formyl-Met-Leu-Phe (fMLP) induced reactive oxygen species production. Neutrophil rolling, arrest, and migration was assessed in vascular mimetic microfluidic channels coated with E-selectin and ICAM-1 to simulate inflamed endothelium. Neutrophils exposed to Feraheme rolled faster on E-selectin and arrested less frequently on ICAM-1, in a manner dependent upon SPION concentration. Subsequent neutrophil shape change, and migration were also significantly inhibited in the presence of Feraheme. Lastly, Feraheme accelerated clearance of cytosolic calcium flux following IL-8 stimulation. We conclude that uptake of Feraheme by neutrophils inhibits chemotactic activation and downregulates normal rolling to arrest under shear flow. The mechanism involves increased calcium clearance following chemotactic activation, which may diminish the efficiency of recruitment from the circulation at vascular sites of inflammation.

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Neutrophil-Mediated Transport is Crucial for Short-Circulating Magnetic Nanoparticles Delivery to Tumors

Cited by 2 publications

References 0 publications

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Neutrophil Inflammatory Response Is Downregulated by Uptake of Superparamagnetic Iron Oxide Nanoparticle Therapeutics

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