Abstract 4248: Functional imaging markers for blockade of breast cancer metastasis by IGF1R and insulin receptor targeted drugs using novel MRI and targeted iron oxide nanoparticles

Author(s):  
Deepali Sachdev ◽  
Huy Donguyen ◽  
Naoharu Kobayashi ◽  
Sidath C. Kumarapperuma ◽  
Joeseph C. Weber
2020 ◽  
Vol 13 ◽  
Author(s):  
Selin Yılmaz ◽  
Çiğdem İçhedef ◽  
Kadriye Buşra Karatay ◽  
Serap Teksöz

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.


2015 ◽  
Vol 15 (12) ◽  
pp. 9464-9472 ◽  
Author(s):  
Sougata Ghosh ◽  
Piyush More ◽  
Abhishek Derle ◽  
Rohini Kitture ◽  
Trupti Kale ◽  
...  

2006 ◽  
Vol 99 (2) ◽  
pp. 163-176 ◽  
Author(s):  
Carola Leuschner ◽  
Challa SSR Kumar ◽  
William Hansel ◽  
Wole Soboyejo ◽  
Jikou Zhou ◽  
...  

2004 ◽  
Vol 24 (22) ◽  
pp. 9726-9735 ◽  
Author(s):  
Julie A. Nagle ◽  
Zhefu Ma ◽  
Maura A. Byrne ◽  
Morris F. White ◽  
Leslie M. Shaw

ABSTRACT The insulin receptor substrate (IRS) proteins are adaptor molecules that integrate signals generated by receptors that are implicated in human breast cancer. We investigated the specific contribution of IRS-2 to mammary tumor progression using transgenic mice that express the polyoma virus middle T antigen (PyV-MT) in the mammary gland and IRS-2-null (IRS-2−/−) mice. PyV-MT-induced tumor initiation and growth were similar in wild-type (WT) and IRS-2−/− mice. However, the latency and incidence of metastasis were significantly decreased in the absence of IRS-2 expression. The contribution of IRS-2 to metastasis is intrinsic to the tumor cells, because IRS-2−/− mammary tumor cells did not metastasize when grown orthotopically in the mammary fat pads of WT mice. WT and IRS-2−/− tumors contained similar numbers of mitotic cells, but IRS-2−/− tumors had a higher incidence of apoptosis than did WT tumors. In vitro, IRS-2−/− mammary tumor cells were less invasive and more apoptotic in response to growth factor deprivation than their WT counterparts. In contrast, IRS-1−/− tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis.


2018 ◽  
Vol Volume 14 ◽  
pp. 161-180 ◽  
Author(s):  
Stephan Lugert ◽  
Harald Unterweger ◽  
Marina Mühlberger ◽  
Christina Janko ◽  
Sebastian Draack ◽  
...  

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