TY - JOUR
T1 - Radiolabeled Biodistribution of Expansile Nanoparticles
T2 - Intraperitoneal Administration Results in Tumor Specific Accumulation
AU - Colby, Aaron H.
AU - Kirsch, Jack
AU - Patwa, Amit N.
AU - Liu, Rong
AU - Hollister, Beth
AU - McCulloch, William
AU - Burdette, Joanna E.
AU - Pearce, Cedric J.
AU - Oberliels, Nicholas H.
AU - Colson, Yolonda L.
AU - Liu, Kebin
AU - Grinstaff, Mark W.
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/2/14
Y1 - 2023/2/14
N2 - Nanoparticle biodistribution in vivo is an essential component to the success of nanoparticle-based drug delivery systems. Previous studies with fluorescently labeled expansile nanoparticles, or “eNPs”, demonstrated a high specificity of eNPs to tumors that is achieved through a materials-based targeting strategy. However, fluorescent labeling techniques are primarily qualitative in nature and the gold-standard for quantitative evaluation of biodistribution is through radiolabeling. In this manuscript, we synthesize 14C-labeled eNPs to quantitatively evaluate the biodistribution of these particles in a murine model of intraperitoneal mesothelioma via liquid scintillation counting. The results demonstrate a strong specificity of eNPs for tumors that lasts one to 2 weeks postinjection with an overall delivery efficiency to the tumor tissue of 30% of the injected dose which is congruent with prior reports of preclinical efficacy of the technology. Importantly, the route of administration is essential to the eNP’s material-based targeting strategy with intraperitoneal administration leading to tumoral accumulation while, in contrast, intravenous administration leads to rapid clearance via the reticuloendothelial system and low tumoral accumulation. A comparison against nanoparticle delivery systems published over the past decade shows that the 30% tumoral delivery efficiency of the eNP is significantly higher than the 0.7% median delivery efficiency of other systems with sufficient quantitative data to define this metric. These results lay a foundation for targeting intraperitoneal tumors and encourage efforts to explore alternative, nonintravenous routes, of delivery to accelerate the translation of nanoparticle therapies to the clinic.
AB - Nanoparticle biodistribution in vivo is an essential component to the success of nanoparticle-based drug delivery systems. Previous studies with fluorescently labeled expansile nanoparticles, or “eNPs”, demonstrated a high specificity of eNPs to tumors that is achieved through a materials-based targeting strategy. However, fluorescent labeling techniques are primarily qualitative in nature and the gold-standard for quantitative evaluation of biodistribution is through radiolabeling. In this manuscript, we synthesize 14C-labeled eNPs to quantitatively evaluate the biodistribution of these particles in a murine model of intraperitoneal mesothelioma via liquid scintillation counting. The results demonstrate a strong specificity of eNPs for tumors that lasts one to 2 weeks postinjection with an overall delivery efficiency to the tumor tissue of 30% of the injected dose which is congruent with prior reports of preclinical efficacy of the technology. Importantly, the route of administration is essential to the eNP’s material-based targeting strategy with intraperitoneal administration leading to tumoral accumulation while, in contrast, intravenous administration leads to rapid clearance via the reticuloendothelial system and low tumoral accumulation. A comparison against nanoparticle delivery systems published over the past decade shows that the 30% tumoral delivery efficiency of the eNP is significantly higher than the 0.7% median delivery efficiency of other systems with sufficient quantitative data to define this metric. These results lay a foundation for targeting intraperitoneal tumors and encourage efforts to explore alternative, nonintravenous routes, of delivery to accelerate the translation of nanoparticle therapies to the clinic.
KW - Radiolabeled biodistribution
KW - expansile nanoparticle
KW - intraperitoneal administration
KW - liquid scintillation counting
KW - materials-based targeting
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U2 - 10.1021/acsnano.2c08451
DO - 10.1021/acsnano.2c08451
M3 - Article
C2 - 36701244
AN - SCOPUS:85147167511
SN - 1936-0851
VL - 17
SP - 2212
EP - 2221
JO - ACS Nano
JF - ACS Nano
IS - 3
ER -