Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer

Rosenberger, Ina; Strauss, Albert; Dobiasch, Sophie; Weis, Christian; Szanyi, Szilárd; Gil-Iceta, L.; Alonso, Eduardo; Esparza, M. González; Gómez‐Vallejo, Vanessa; Szczupak, Bogusław; Plaza-García, Sandra; Mirzaei, Siroos; Israel, L.; Bianchessi, Silvia; Scanziani, Eugenio; Lellouche, Jean‐Paul; Kabos, Peter; Werner, Jens; Felix, Klaus; Grenacher, Lars; Reese, Torsten; Kreuter, Jörg; Jiménez-González, María

doi:10.1016/j.jconrel.2015.07.017

Cited by 55 publications

(24 citation statements)

References 21 publications

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“…Here, as a proof of principle, we used a vectorized nanodiagnostic without a warhead (therapeutic cargo of anticancer drug) and were able to demonstrate that such particles are more efficiently deposed in pancreatic s.c. tumor models in comparison with NPs without outer shell [32]. Additionally, applying MRI we could demonstrate that a more efficient NP deposition was observed in orthotopic tumors in comparison with the subcutaneous tumors.…”

Section: Discussionmentioning

confidence: 96%

“…As a positive follow-up of our previous report [32], we here explored the potential of vectorized biodegradable nanoparticles with an outer protective PEG shell cleavable by MMPs. Through this removable coating the NPs were less filtered out by the monocyte phagocytic system and resided for extended time in the blood circulation.…”

Section: Discussionmentioning

confidence: 99%

“…For the orthotopic (ortho) tumor model tumor cell inoculation was performed by direct injection of tumor cells in the pancreatic tail of 5 to 6-week-old female CD ® nuBR mice according to the procedure previously described in detail [32]. Briefly, a laparotomy was performed, the spleen with tail of the pancreas was exteriorized with cotton swabs, and with an insulin syringe 27G × 1.2 in., 1.0 ml (Terumo, Eschborn, Germany) approx.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

et al. 2016

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BackgroundFunctionalized nanoparticles (NPs) are one promising tool for detecting specific molecular targets and combine molecular biology and nanotechnology aiming at modern imaging. We aimed at ligand-directed delivery with a suitable target-biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising targets are galectins (Gal), due to their strong expression in and on PDAC-cells and occurrence at early stages in cancer precursor lesions, but not in adjacent normal tissues.ResultsMolecular probes (10-29 AA long peptides) derived from human tissue plasminogen activator (t-PA) were selected as binding partners to galectins. Affinity constants between the synthesized t-PA peptides and Gal were determined by microscale thermophoresis. The 29 AA-long t-PA-peptide-1 with a lactose-functionalized serine revealed the strongest binding properties to Gal-1 which was 25-fold higher in comparison with the native t-PA protein and showed additional strong binding to Gal-3 and Gal-4, both also over-expressed in PDAC. t-PA-peptide-1 was selected as vector moiety and linked covalently onto the surface of biodegradable iron oxide nanoparticles (NPs). In particular, CAN-doped maghemite NPs (CAN-Mag), promising as contrast agent for magnetic resonance imaging (MRI), were selected as magnetic core and coated with different biocompatible polymers, such as chitosan (CAN-Mag-Chitosan NPs) or polylactic co glycolic acid (PLGA) obtaining polymeric nanoparticles (CAN-Mag@PNPs), already approved for drug delivery applications. The binding efficacy of t-PA-vectorized NPs determined by exposure to different pancreatic cell lines was up to 90%, as assessed by flow cytometry. The in vivo targeting and imaging efficacy of the vectorized NPs were evaluated by applying murine pancreatic tumor models and assessed by 1.5 T magnetic resonance imaging (MRI). The t-PA-vectorized NPs as well as the protease-activated NPs with outer shell decoration (CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac) showed clearly detectable drop of subcutaneous and orthotopic tumor staining-intensity indicating a considerable uptake of the injected NPs. Post mortem NP deposition in tumors and organs was confirmed by Fe staining of histopathology tissue sections.ConclusionsThe targeted NPs indicate a fast and enhanced deposition of NPs in the murine tumor models. The CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac interlocking steps strategy of NPs delivery and deposition in pancreatic tumor is promising.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

et al. 2016

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“…A number of of the magnetic nanostructures can be used in medical applications due to their non-toxicity and biocompatibility [1][2][3]. Several studies have been performed into the use of the materials in drug delivery [4,5], magnetic resonance imaging (MRI) [6], hyperthermia [7,8], medical diagnosis and therapy [9,10] gas sensors [11][12][13], catalysts [14,15], and environmental remediation [16,17]. Several methods are used to synthesize magnetic material; e.g., sol-gel [18,19], reverse micelle [20], co-precipitation process [21,22], γ-ray irradiation [23,24], non-aqueous route [25], microwave plasma synthesis [26], and hydrothermal treatment [27,28].…”

Section: Introductionmentioning

confidence: 99%

Solvothermal synthesis of porous Fe₃O₄ nanoparticles for humidity sensor application

Zak

Shirmahd

Mohammadi

et al. 2020

Mater. Res. Express

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In this research, the effect of PVP on magnetic properties and morphology of Fe 3 O 4 nanoparticle (Fe 3 O 4 -NP S ) is investigated. Also, the sensitivity of the humidity of the selected Fe 3 O 4 -NP S is studied. X-ray diffraction (XRD), transmission electron microscope (TEM), and vibration sample magnetometer (VSM) were used to characterize the synthesized Fe 3 O 4 -NPs. The XRD and TEM results demonstrated that Fe 3 O 4 -NPs were crystallized in cubic structure with spherical pores morphology. Superparamagnetic behavior was seen in the samples prepared with the maximum saturation of approximately 10 emu g −1 for the sample synthesized using PVP:Fe(ac ac) 3 ratio equal to 4. The outcomes of the humidity sensing of the selected sample revealed that the prepared Fe 3 O 4 -NPs with a porous structure is a good candidate to be used for humidity sensing.

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“…Over the years, nanotechnology biomedical applications have opened a window in the research of new diagnostic and therapeutic settings for HCC and PAC [4,5]. Among the different nanoparticles available, iron oxide nanoparticles (IONs) have received extensive attention due to their availability and properties.…”

Section: Introductionmentioning

confidence: 99%

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas: a feasibility study in pigs.

et al. 2016

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Aims: Pancreatic cancer and hepatocellular carcinoma are two of the most aggressive types of cancer with limited therapeutic options in stages of advanced disease. Our objective is to assess the safety and feasibility of injecting iron oxide nanoparticles (IONs) via endoscopic ultrasound (EUS)-guidance, both systemically and locally in the liver and pancreas in order to study new potential therapies for liver and pancreatic tumors. Material and methods: Six domestic pigs were used for our study design, and divided into three groups: two were injected in the portal vein, and other four were subjected to local exposure of IONs in the liver and pancreas, two each. The pigs were on a 7 days follow-up and necropsy was performed with their organs harvested. A 3T MRI scan was also performed. Results: All animals underwent an endoscopic ultrasound fine needle injection (EUS-FNI) procedure without any complications. EUS-FNI procedure had an average time of 5 minutes and 21 seconds and consisted of 2 ml of ION injection. No perforations and no risk of potential bleeding were recorded. Macroscopic changes were observed only after pancreatic EUS-FNI. A significant amount of IONs was observed in the liver after local injection and after vascular EUS-FNI. The imaging results were confirmed by pathological examination with most of the IONs accumulated in Ito-like cells, Kupfer cells, and sinusoids. Conclusions: IONs have been widely studied for both diagnostic and therapeutic purposes. Their injection through EUS-guidance may develop new diagnosis strategies as well as curative or palliative therapies in pancreatic and liver tumors.

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Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer

Cited by 55 publications

References 21 publications

Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

Solvothermal synthesis of porous Fe₃O₄ nanoparticles for humidity sensor application

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas: a feasibility study in pigs.

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Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer

Cited by 55 publications

References 21 publications

Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer

Solvothermal synthesis of porous Fe3O4 nanoparticles for humidity sensor application

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas: a feasibility study in pigs.

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Solvothermal synthesis of porous Fe₃O₄ nanoparticles for humidity sensor application