Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses
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Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses. / Wyss, Pradeep P; Lamichhane, Surya P; Abed, Ahmed; Vonwil, Daniel; Kretz, Oliver; Huber, Tobias B; Sarem, Melika; Shastri, V Prasad.
In: BIOMATERIALS, Vol. 230, 02.2020, p. 119643.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses
AU - Wyss, Pradeep P
AU - Lamichhane, Surya P
AU - Abed, Ahmed
AU - Vonwil, Daniel
AU - Kretz, Oliver
AU - Huber, Tobias B
AU - Sarem, Melika
AU - Shastri, V Prasad
N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - It has been shown that viral particles such as herpes simplex virus-1 and cytomegalovirus show renal clearance despite their large size (155-240 nm). Interestingly, one of the common characteristics of these viruses is their glycoprotein rich viral envelope. Since, glycosaminoglycans (GAGs) share similarities with oligosaccharide chains in the glycoproteins, we hypothesize that modification of nanoparticles (NPs) surface with naturally found GAGs could alter NP clearance characteristics by mimicking physicochemical aspects of viral glycoprotein envelope. We demonstrate that polymeric NP bearing surfaces enriched with dermatan sulfate, chondroitin sulfate, heparin sulfate, and hyaluronic acid undergo rapid renal clearance (74% of injected dose as early as 2 h) while showing reduced liver accumulation. Ultra-structural analyses suggest that the excretion of intact NPs occurs via proximal tubule secretion, but not via glomerular filtration. Finally, we demonstrate that our bioinspired NPs are able to accumulate within the epithelial tumor microenvironment despite their efficient renal clearance. Our system provides a framework to address renal toxicity associated with repeated dosing of NP and a platform to elaborate on plausible mechanism of renal clearance of virus particle.
AB - It has been shown that viral particles such as herpes simplex virus-1 and cytomegalovirus show renal clearance despite their large size (155-240 nm). Interestingly, one of the common characteristics of these viruses is their glycoprotein rich viral envelope. Since, glycosaminoglycans (GAGs) share similarities with oligosaccharide chains in the glycoproteins, we hypothesize that modification of nanoparticles (NPs) surface with naturally found GAGs could alter NP clearance characteristics by mimicking physicochemical aspects of viral glycoprotein envelope. We demonstrate that polymeric NP bearing surfaces enriched with dermatan sulfate, chondroitin sulfate, heparin sulfate, and hyaluronic acid undergo rapid renal clearance (74% of injected dose as early as 2 h) while showing reduced liver accumulation. Ultra-structural analyses suggest that the excretion of intact NPs occurs via proximal tubule secretion, but not via glomerular filtration. Finally, we demonstrate that our bioinspired NPs are able to accumulate within the epithelial tumor microenvironment despite their efficient renal clearance. Our system provides a framework to address renal toxicity associated with repeated dosing of NP and a platform to elaborate on plausible mechanism of renal clearance of virus particle.
U2 - 10.1016/j.biomaterials.2019.119643
DO - 10.1016/j.biomaterials.2019.119643
M3 - SCORING: Journal article
C2 - 31812275
VL - 230
SP - 119643
JO - BIOMATERIALS
JF - BIOMATERIALS
SN - 0142-9612
ER -
