TY - JOUR
T1 - Zonal Intratumoral Delivery of Nanoparticles Guided by Surface Functionalization
AU - Terracciano, Rossana
AU - Carcamo-Bahena, Yareli
AU - Royal, Amber Lee R.
AU - Messina, Luca
AU - Delk, Jack
AU - Butler, E. Brian
AU - Demarchi, Danilo
AU - Grattoni, Alessandro
AU - Wang, Zhihui
AU - Cristini, Vittorio
AU - Dogra, Prashant
AU - Filgueira, Carly S.
N1 - Funding Information:
This study was supported by the Golfers Against Cancer (A.G., E.B.B., and C.S.F.), funds from Houston Methodist Research Institute (C.S.F.), and the Cockrell Foundation (V.C., P.D.). The mathematical modeling work has been supported in part by the National Institutes of Health (NIH) Grants 1R01CA253865 (Z.W., V.C.), 1R01CA226537 (Z.W., V.C.), and 1R01CA222007 (Z.W., V.C.). The authors are grateful to the Houston Methodist Research Institute Electron Microscopy Core, the Houston Methodist Research Institute Translational Imaging PreClinical Imaging (Small Animal) Core, and the Houston Methodist Research Institute Research Pathology Core for their assistance with the electron microscope, in vivo imaging experiments, and histological sample preparation and evaluations, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/11/15
Y1 - 2022/11/15
N2 - Delivery of small molecules and anticancer agents to malignant cells or specific regions within a tumor is limited by penetration depth and poor spatial drug distribution, hindering anticancer efficacy. Herein, we demonstrate control over gold nanoparticle (GNP) penetration and spatial distribution across solid tumors by administering GNPs with different surface chemistries at a constant injection rate via syringe pump. A key finding in this study is the discovery of different zone-specific accumulation patterns of intratumorally injected nanoparticles dependent on surface functionalization. Computed tomography (CT) imaging performed in vivo of C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors on their flank and gross visualization of excised tumors consistently revealed that intratumorally administered citrate-GNPs accumulate in particle clusters in central areas of the tumor, while GNPs functionalized with thiolated phosphothioethanol (PTE-GNPs) and thiolated polyethylene glycol (PEG-GNPs) regularly accumulate in the tumor periphery. Further, PEG functionalization resulted in larger tumoral surface coverage than PTE, reaching beyond the outer zone of the tumor mass and into the surrounding stroma. To understand the dissimilarities in spatiotemporal evolution across the different GNP surface chemistries, we modeled their intratumoral transport with reaction-diffusion equations. Our results suggest that GNP surface passivation affects nanoparticle reactivity with the tumor microenvironment, leading to differential transport behavior across tumor zones. The present study provides a mechanistic understanding of the factors affecting spatiotemporal distribution of nanoparticles in the tumor. Our proof of concept of zonal delivery within the tumor may prove useful for directing anticancer therapies to regions of biomarker overexpression.
AB - Delivery of small molecules and anticancer agents to malignant cells or specific regions within a tumor is limited by penetration depth and poor spatial drug distribution, hindering anticancer efficacy. Herein, we demonstrate control over gold nanoparticle (GNP) penetration and spatial distribution across solid tumors by administering GNPs with different surface chemistries at a constant injection rate via syringe pump. A key finding in this study is the discovery of different zone-specific accumulation patterns of intratumorally injected nanoparticles dependent on surface functionalization. Computed tomography (CT) imaging performed in vivo of C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors on their flank and gross visualization of excised tumors consistently revealed that intratumorally administered citrate-GNPs accumulate in particle clusters in central areas of the tumor, while GNPs functionalized with thiolated phosphothioethanol (PTE-GNPs) and thiolated polyethylene glycol (PEG-GNPs) regularly accumulate in the tumor periphery. Further, PEG functionalization resulted in larger tumoral surface coverage than PTE, reaching beyond the outer zone of the tumor mass and into the surrounding stroma. To understand the dissimilarities in spatiotemporal evolution across the different GNP surface chemistries, we modeled their intratumoral transport with reaction-diffusion equations. Our results suggest that GNP surface passivation affects nanoparticle reactivity with the tumor microenvironment, leading to differential transport behavior across tumor zones. The present study provides a mechanistic understanding of the factors affecting spatiotemporal distribution of nanoparticles in the tumor. Our proof of concept of zonal delivery within the tumor may prove useful for directing anticancer therapies to regions of biomarker overexpression.
UR - http://www.scopus.com/inward/record.url?scp=85141622019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141622019&partnerID=8YFLogxK
U2 - 10.1021/acs.langmuir.2c02319
DO - 10.1021/acs.langmuir.2c02319
M3 - Article
C2 - 36318182
SN - 0743-7463
VL - 38
SP - 13983
EP - 13994
JO - Langmuir
JF - Langmuir
IS - 45
ER -