Nanoparticles often only exploit the upregulation of a receptor on cancer cells to enhance intratumoral deposition of therapeutic and imaging agents. However, a single targeting moiety assumes that a tumor is homogenous and static. Tumoral microenvironments are both heterogenous and dynamic, often displaying variable spatial and temporal expression of targetable receptors throughout disease progression. Here, we evaluated the in vivo performance of an iron oxide nanoparticle in terms of targeting and imaging of orthotropic mouse models of aggressive breast tumors. The nanoparticle, a multi-component nanochain, was comprised of 3–5 iron oxide nanoparticles chemically linked in a linear chain. The nanoparticle’s surface was decorated with two types of ligands each targeting two different upregulated biomarkers on the tumor endothelium, P-selectin and fibronectin. The nanochain exhibited improved tumor deposition not only through vascular targeting but also through its elongated structure. A single-ligand nanochain exhibited a ~2.5-fold higher intratumoral deposition than a spherical nanoparticle variant. Furthermore, the dual-ligand nanochain exhibited higher consistency in generating detectable MR signals compared to a single-ligand nanochain. Using a 7T MRI, the dual-ligand nanochains exhibited highly detectable MR signal within 3h after injection in two different animal models of breast cancer.
Chronic exposure to particulate matter < 2.5µ (PM 2.5) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (AΦ) are long-lived, self-renew and critical to the health impact of inhalational insults. There is an inadequate understanding of the impact of PM 2.5 exposure on the nature/time course of transcriptional responses, self-renewal of AΦ, and the contribution from bone marrow (BM) to this population. Accordingly, we exposed chimeric (CD45.2/CD45.1) mice to concentrated PM 2.5 or filtered air (FA) to evaluate the impact on these end-points. PM 2.5 exposure for 4-weeks induced an influx of BM-derived monocytes into the lungs with no contribution to the overall TR-AΦ pool. Chronic (32-weeks) PM 2.5 exposure on the other hand while associated with increased recruitment of BM-derived monocytes and their incorporation into the AΦ population, resulted in enhanced apoptosis and decreased proliferation of TR-AΦ. RNA-seq analysis of isolated TR-AΦ and BM-AΦ from 4-and 32-weeks exposed mice revealed a unique time-dependent pattern of differentially expressed genes. PM 2.5 exposure resulted in altered histological changes in the lungs, a reduced alveolar fraction which corresponded to protracted lung inflammation. Our findings suggest a time-dependent entrainment of BM-derived monocytes into the AΦ population of PM 2.5 exposed mice, that together with enhanced apoptosis of TR-AΦ and reorganization of transcriptional responses, could collectively contribute to the perpetuation of chronic inflammation. Exposure to ambient air pollution, specifically particulate matter < 2.5 µm in diameter (PM 2.5) is the world's leading environmental risk factor for non-communicable diseases, including respiratory disorders. Inhalational exposure to PM 2.5 has been implicated in adverse health outcomes across the lifespan, including impaired lung development, acceleration of age-related decline in lung function, pulmonary and cardiovascular disorders 1. The alveolar macrophage (AΦ) population in the lung are the first line of defense, responsible for the phagocytosis of inhaled particles and maintenance of immune homeostasis in the lung.
Iron oxide nanoparticles (IONPs) have often been investigated for tumor hyperthermia. IONPs act as heating foci in the presence of an alternating magnetic field (AMF). It has been shown that...
15 16 17 18 19 20 21 22 23 24 25 ABSTRACT26 Nanoparticles often only exploit the upregulation of a receptor on cancer cells to enhance 27 intratumoral deposition of therapeutic and imaging agents. However, a single targeting moiety 28 assumes that a tumor is homogenous and static. Tumoral microenvironments are both 29 heterogenous and dynamic, often displaying variable spatial and temporal expression of 30 targetable receptors throughout disease progression. Here, we evaluated the in vivo performance 31 of an iron oxide nanoparticle in terms of targeting and imaging of orthotropic mouse models of 32 aggressive breast tumors. The nanoparticle, a multi-component nanochain, was comprised of 3-33 5 iron oxide nanoparticles chemically linked in a linear chain. The nanoparticle's surface was 34 decorated with two types of ligands each targeting two different upregulated biomarkers on the 35 tumor endothelium, P-selectin and fibronectin. The nanochain exhibited improved tumor 36 deposition not only through vascular targeting but also through its elongated structure. A single-37 ligand nanochain exhibited a ~2.5-fold higher intratumoral deposition than a spherical 38 nanoparticle variant. Furthermore, the dual-ligand nanochain exhibited higher consistency in 39 generating detectable MR signals compared to a single-ligand nanochain. Using a 7T MRI, the 40 dual-ligand nanochains exhibited highly detectable MR signal within 3h after injection in two 41 different animal models of breast cancer. 42 43 44 45 KEYWORDS 46 Iron oxide nanochains; dual-ligand nanoparticle; breast cancer, MRI 47 48 49 50 51 52 53 54 INTRODUCTION 55Imaging is critical for management of patients with breast cancer including diagnosis, 56 treatment planning and response assessments. To improve cancer imaging, various targeting 57 schemes have been employed to direct nanoparticle imaging agents to cancers [1, 2]. Traditional 58 targeting strategies decorate the surface of nanoparticles with a ligand directing them to 59 upregulated receptors on breast cancer cells within the tumor interstitium. Rather than targeting 60 the tumor interstitium, an alternative strategy is to use vascular targeting and direct the 61 nanoparticles to the altered endothelium associated with breast cancer. The endothelium of 62 tumors, including those of the breast, displays a wide variety of targetable biomarkers that are not 63 readily found on healthy endothelium. For circulating nanoparticles, the endothelium is the closest 64 point-of-contact, which facilitates direct access to the targetable vascular biomarkers of the 65 disease [3-9]. Considering their size and multivalent avidity, nanoparticles are ideal for vascular 66 targeting. 67Further, the shape of the nanoparticle can dictate its targeting avidity [7,[10][11][12]. Recently, 68 we reported a new one-pot synthetic concept for making multicomponent chain-like nanoparticles 69 (termed nanochains), which are comprised of about three iron oxide nanospheres chemically 70 linked into a linear, chain-like assembly [13]. ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.