TY - JOUR
T1 - Size-Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature-Based Differential Targeting in Triple Negative Breast Cancer
AU - Goel, Shreya
AU - Ferreira, Carolina A.
AU - Dogra, Prashant
AU - Yu, Bo
AU - Kutyreff, Christopher J.
AU - Siamof, Cerise M.
AU - Engle, Jonathan W.
AU - Barnhart, Todd E.
AU - Cristini, Vittorio
AU - Wang, Zhihui
AU - Cai, Weibo
N1 - Funding Information:
S.G., C.A.F, and P.D. contributed equally to this work. This work was supported by the University of Wisconsin – Madison and the National Institutes of Health P30CA014520, and the Brazilian Science without Borders Program SwB‐CNPq. This research was also supported in part by the National Science Foundation Grant DMS‐1716737, the National Institutes of Health (NIH) Grants 1U01CA196403, 1U01CA213759, 1R01CA226537, 1R01CA222007, and U54CA210181.
Funding Information:
S.G., C.A.F, and P.D. contributed equally to this work. This work was supported by the University of Wisconsin ? Madison and the National Institutes of Health P30CA014520, and the Brazilian Science without Borders Program SwB-CNPq. This research was also supported in part by the National Science Foundation Grant DMS-1716737, the National Institutes of Health (NIH) Grants 1U01CA196403, 1U01CA213759, 1R01CA226537, 1R01CA222007, and U54CA210181.
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12–15 nm) porous silica nanoparticles (UPSNs), capable of prolonged plasma half-life, attenuated RES sequestration, and accelerated hepatobiliary clearance, is reported. The study further investigates the effect of tumor vascularization on uptake and retention of UPSNs in two mouse models of triple negative breast cancer with distinctly different microenvironments. A semimechanistic mathematical model is developed to gain mechanistic insights into the interactions between the UPSNs and the biological entities of interest, specifically the RES. Despite similar systemic pharmacokinetic profiles, UPSNs demonstrate strikingly different tumor responses in the two models. Histopathology confirms the differences in vasculature and stromal status of the two models, and corresponding differences in the microscopic distribution of UPSNs within the tumors. The studies demonstrate the successful application of multidisciplinary and complementary approaches, based on laboratory experimentation and mathematical modeling, to concurrently design optimized nanomaterials, and investigate their complex biological interactions, in order to drive innovation and translation.
AB - Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12–15 nm) porous silica nanoparticles (UPSNs), capable of prolonged plasma half-life, attenuated RES sequestration, and accelerated hepatobiliary clearance, is reported. The study further investigates the effect of tumor vascularization on uptake and retention of UPSNs in two mouse models of triple negative breast cancer with distinctly different microenvironments. A semimechanistic mathematical model is developed to gain mechanistic insights into the interactions between the UPSNs and the biological entities of interest, specifically the RES. Despite similar systemic pharmacokinetic profiles, UPSNs demonstrate strikingly different tumor responses in the two models. Histopathology confirms the differences in vasculature and stromal status of the two models, and corresponding differences in the microscopic distribution of UPSNs within the tumors. The studies demonstrate the successful application of multidisciplinary and complementary approaches, based on laboratory experimentation and mathematical modeling, to concurrently design optimized nanomaterials, and investigate their complex biological interactions, in order to drive innovation and translation.
KW - mathematical modeling
KW - pharmacokinetics
KW - positron emission tomography
KW - tumor microenvironment
KW - ultrasmall porous silica
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U2 - 10.1002/smll.201903747
DO - 10.1002/smll.201903747
M3 - Article
C2 - 31565854
AN - SCOPUS:85073982289
SN - 1613-6810
VL - 15
SP - e1903747
JO - Small
JF - Small
IS - 46
M1 - 1903747
ER -