Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

Abstract Background: Pancreatic cancer (PC) is one of the most devastating types of cancers worldwide and has a remarkably poor survival rate, emphasizing the need for more effective strategies for the diagnosis and therapy of PC. Upconversion nanoparticles (UCNPs) have gained a privileged place in the biomedical field due to their outstanding properties. Besides, epithelial cell adhesion molecule (EpCAM) as one of the key biomarkers of pancreatic cancer stem cells, is a vital target for theranostic, diagnostic, and/or therapeutic intervention in nanomedicine. In this study, the theranostic nanosystem (EpCAM-UCMSNs-MX) was formed from the mesoporous silica-coated UCNPs functionalized with anti-EpCAM monoclonal antibody, and then one anticancer drug and photosensitizer, mitoxantrone (MX), was loaded into the mesoporous silica. The nanotheranostic system was used to target caner stem cells for realizing simultaneous dual-modality MR/UCL imaging and synergetic chemotherapy and NIR-triggered PDT. Results: After conducting series of characterizations, the nanotheranostic systems own superior uniform sphericity and long-time stability. In vitro and vivo experiments show the nanocomposites have good biocompatibility and can target caner stem cells to realize simultaneous dual-modality MR/UCL imaging. Furthermore, in comparison with UCMSNs-MX and free MX, MX-loaded UCMSNs conjugated with anti-EpCAM monoclonal antibody (EpCAM-UCMSNs-MX) are efficiently endocytosed by cancerous cells and show synergetic effect with PDT in vitro. In vivo experiments reconfirm the synergistic effects observed with the combination of EpCAM-UCMSNs-MX and PDT, which results in better treatment outcomes as compared to chemotherapy or NIR irradiation alone that fail to show any noticeable systemic toxicity.Conclusions: The resulting nanotheranostics were shown to target caner stem cells to confer simultaneous dual-modality MR/UCL imaging and induced intracellular reactive oxygen species exposed to 980 nm excitation, leading to synergetic chemotherapy and NIR-triggered PDT. These results offer a promising strategy for designing a multifunctional nanotheranostic system for dual-modality imaging-guided synergistic oncotherapy.

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Faculty Opinions recommendation of In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13372017.14742134 ◽

2011 ◽

Author(s):

Peter Harvison

Keyword(s):

Drug Transporters ◽

In Vivo Assessment

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In vitro and in vivo assessment of biocompatibility of AZ31 alloy as biliary stents: a preclinical approach

Archives of Medical Science ◽

10.5114/aoms.2020.92675 ◽

2020 ◽

Author(s):

Yong Song ◽

Gaoping Qin ◽

Lixue Du ◽

Haitian Hu ◽

Yong Han

Keyword(s):

Az31 Alloy ◽

Biliary Stents ◽

In Vivo Assessment

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In vivo assessment of a single adenine mutation in 5′UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study

BMC Research Notes ◽

10.1186/s13104-021-05609-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Abhishek Kumar ◽

Minati Choudhury ◽

Sakshi Dhingra Batra ◽

Kriti Sikri ◽

Anushree Gupta

Keyword(s):

Pulmonary Hypertension ◽

Congenital Heart ◽

Small Sample Size ◽

Small Sample ◽

Severe Pulmonary Hypertension ◽

Endothelin 1 ◽

Circulating Levels ◽

In Vivo Assessment

Abstract Objective Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 ‘A’, adenine insertion variant in 5′UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. Results The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 ‘A’ insertion variant in 5′UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted ‘A’ allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

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Immunocompatibility of a new dual modality contrast agent based on radiolabeled iron-oxide nanoparticles

Scientific Reports ◽

10.1038/s41598-021-89117-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria-Argyro Karageorgou ◽

Dimosthenis Stamopoulos

Keyword(s):

Complete Blood Count ◽

Morphological Characteristics ◽

Mononuclear Phagocyte ◽

Dual Modality ◽

Immunodeficient Mice ◽

Force Microscopy ◽

Magnetic Resonance Imaging Mri ◽

Diagnostic Applications

AbstractRadiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. The immunocompatibility of a new DMCA is a prerequisite for subsequent in vivo applications. Here, a new DMCA, namely Fe3O4 nanoparticles radiolabeled with 68Ga, is subjected to immunocompatibility tests both in vitro and in vivo. The in vitro immunocompatibility of the DMCA relied on incubation with donated human WBCs and PLTs (five healthy individuals). Optical microscopy (OM) and atomic force microscopy (AFM) were employed for the investigation of the morphological characteristics of WBCs and PLTs. A standard hematology analyzer (HA) provided information on complete blood count. The in vivo immunocompatibility of the DMCA was assessed through its biodistribution among the basic organs of the mononuclear phagocyte system in normal and immunodeficient mice (nine in each group). In addition, Magnetic Resonance Imaging (MRI) data were acquired in normal mice (three). The combined OM, AFM and HA in vitro data showed that although the DMCA promoted noticeable activation of WBCs and PLTs, neither degradation nor clustering were observed. The in vivo data showed no difference of the DMCA biodistribution between the normal and immunodeficient mice, while the MRI data prove the efficacy of the particular DMCA when compared to the non-radiolabeled, parent CA. The combined in vitro and in vivo data prove that the particular DMCA is a promising candidate for future in vivo applications.

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