scholarly journals 2422

2017 ◽  
Vol 1 (S1) ◽  
pp. 9-9
Author(s):  
Adam Grippin ◽  
Elias Sayour ◽  
Jon Dobson ◽  
Duane A. Mitchell

OBJECTIVES/SPECIFIC AIMS: Immune-based therapies hold great promise for treatment of refractory tumors. However, development is limited by a lack of identified immune correlates to vaccination. We recently showed that dendritic cells (DCs) prolong progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, and that DC migration to site draining lymph nodes robustly correlates with both PFS and OS. While this appears to be a reliable immune correlate, the complexity of routine labeling for PET and SPECT prohibits validation in a large clinical study. We therefore seek to develop a safe, translatable reporter that can be imaged with a widely available imaging modality. METHODS/STUDY POPULATION: The cationic liposome 1,2-doleoyl-3-trimethylammonium-propane (DOTAP) was loaded with MRI-imageable iron oxide nanoparticles (IONPs) with or without the neutral molecules PEG and cholesterol. The resulting nanoparticles were loaded with RNA to form RNA-NPs that were characterized with transmission electron microscopy (TEM) and used to transfect DCs in vitro; 4.7 T MRI was then used to image particles or cells in agarose gel phantoms. RESULTS/ANTICIPATED RESULTS: TEM images of RNA-NPs indicate the presence of IONP-loaded liposomes. In vitro transfection experiments demonstrate that iron oxide does not reduce RNA-NP-mediated transfection of DCs. Additionally, small amounts of either PEG or cholesterol within RNA-NPs increased transfection of DC2.4s and enhanced T-cell priming by bone marrow-derived dendritic cells. A series of 4.7 T MRI images of particles in cells, spleens, and LNs demonstrated quantifiable differences in particle density between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that IONP-loaded RNA-NPs can be imaged with MRI and manipulated to augment DC function. Future work will include in vivo imaging in mice and safety studies to facilitate translation into first-in-human studies. Successful completion of this project would provide a powerful clinical tool to improve and track patient responses to immune therapy.

MRS Advances ◽  
2019 ◽  
Vol 4 (46-47) ◽  
pp. 2461-2470 ◽  
Author(s):  
Majid Badieirostami ◽  
Colin Carpenter ◽  
Guillem Pratx ◽  
Lei Xing ◽  
Conroy Sun

ABSTRACTNear infrared (NIR) optical imaging has demonstrated significant potential as an effective modality for cancer molecular imaging. Among various NIR probes currently under investigation, upconversion nanophosphors (UCNPs) possess great promise due to their anti-Stokes emission and sequential photon absorption which result in superior detection sensitivity and a simple imaging setup, respectively. Here we investigated the utility of this imaging modality to detect tumor cells expressing the epidermal growth factor receptor (EGFR) using affibody functionalized nanophosphors and a custom built imaging system. Initially, aqueous dispersible NaYF4: Tm+3, Yb+3 UCNPs were synthesized and their photophysical properties were characterized. Then, their luminescence response as a function of concentration and their depth resolving capability in a tissue-simulating phantom were examined. Finally, we demonstrated the use of bioconjugated UCNPs for imaging EGFR-expressing tumors both in vitro and in vivo. Our data suggests that NIR imaging with UCNPs may be useful for noninvasive imaging of tumors.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhou Fang ◽  
Junjian Chen ◽  
Ye Zhu ◽  
Guansong Hu ◽  
Haoqian Xin ◽  
...  

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Miebach ◽  
Eric Freund ◽  
Stefan Horn ◽  
Felix Niessner ◽  
Sanjeev Kumar Sagwal ◽  
...  

AbstractRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.


2015 ◽  
pp. 323 ◽  
Author(s):  
Phuc Pham ◽  
Sinh Nguyen ◽  
Viet Pham ◽  
Ngoc Phan ◽  
Huyen Nguyen ◽  
...  

2008 ◽  
Vol 180 (3) ◽  
pp. 1462-1470 ◽  
Author(s):  
Claudia Papewalis ◽  
Benedikt Jacobs ◽  
Margret Wuttke ◽  
Evelyn Ullrich ◽  
Thomas Baehring ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yang ◽  
Yiming Yang ◽  
Huahua Fan ◽  
Hejian Zou

TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs)in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activityin vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-βproduction was high in the DCiTreg-treated group. DCiTregalso induced new iTregsin vivo. Moreover, the inhibitory activity of DCiTregon CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCsin vivo.


2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.


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