scholarly journals Biodistribution of Poly(alkyl cyanoacrylate) Nanoparticles in Mice and Effect on Tumor Infiltration of Macrophages into a Patient-Derived Breast Cancer Xenograft

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1140
Author(s):  
Abhilash D. Pandya ◽  
Tore-Geir Iversen ◽  
Siver Moestue ◽  
Maria T. Grinde ◽  
Ýrr Mørch ◽  
...  

We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in cellular responses in vitro. The PEBCA NPs had the highest uptake both in the patient-derived breast cancer xenograft MAS98.12 and in lymph nodes, and therefore, they are the most promising of these NPs for delivery of cancer drugs. High-resolution magic angle spinning magnetic resonance (HR MAS MR) spectroscopy did not reveal any differences in the metabolic profiles of tumors following injection of the NPs, but the PEBCA NPs resulted in higher tumor infiltration of the anti-tumorigenic M1 macrophages than obtained with the two other NPs. The PEBCA NPs also increased the ratio of M1/M2 (anti-tumorigenic/pro-tumorigenic) macrophages in the tumors, suggesting that these NPs might be used both as a vehicle for drug delivery and to modulate the immune response in favor of enhanced therapeutic effects.

Metabolites ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 19 ◽  
Author(s):  
Mikheil Gogiashvili ◽  
Jessica Nowacki ◽  
Roland Hergenröder ◽  
Jan G. Hengstler ◽  
Jörg Lambert ◽  
...  

High resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly used for profiling of breast cancer tissue, delivering quantitative information for approximately 40 metabolites. One unique advantage of the method is that it can be used to analyse intact tissue, thereby requiring only minimal sample preparation. Importantly, since the method is non-destructive, it allows further investigations of the same specimen using for instance transcriptomics. Here, we discuss technical aspects critical for a successful analysis — including sample handling, measurement conditions, pulse sequences for one- and two dimensional analysis, and quantification methods - and summarize available studies, with a focus on significant associations of metabolite levels with clinically relevant parameters.


Medicine ◽  
2016 ◽  
Vol 95 (15) ◽  
pp. e3398 ◽  
Author(s):  
Vivian Youngjean Park ◽  
Dahye Yoon ◽  
Ja Seung Koo ◽  
Eun-Kyung Kim ◽  
Seung Il Kim ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 500
Author(s):  
Agnieszka Lis-Cieplak ◽  
Filip Charuk ◽  
Marcin Sobczak ◽  
Anna Zgadzaj ◽  
Agata Drobniewska ◽  
...  

Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used nontoxic β-cyclodextrin (β-CD) as effective, simple, inexpensive, and safe for the human body initiator for the synthesis of biocompatible and biodegradable functionalized polymers suitable for the medical and pharmaceutical applications. The obtained polymeric products were synthesized through a ring-opening polymerization (ROP) of ε-caprolactone (CL), d,l-, and l,l-lactide (LA and LLA). The chemical structures of synthesized materials were elucidated based on 1H NMR and solid-state carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR) analysis, while the incorporation of β-CD molecule into the polymer chain was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, molecular modeling has been applied to investigate the intrachain rigidities and chain architectures for several representative structures. The obtained and thoroughly characterized branched matrices were then used to generate the first β-cyclodextrin/biodegradable polymer/β-blocker conjugate through the successful conjugation of pindolol. The conjugates were fabricated by carbodiimide-mediated coupling reaction. The branched biodegradable materials released the drug in vitro in a sustained manner and without “burst release” and thus have the ability to treat different heart diseases.


2018 ◽  
Vol 115 (13) ◽  
pp. 3237-3242 ◽  
Author(s):  
Anne Diehl ◽  
Yvette Roske ◽  
Linda Ball ◽  
Anup Chowdhury ◽  
Matthias Hiller ◽  
...  

Microorganisms form surface-attached communities, termed biofilms, which can serve as protection against host immune reactions or antibiotics.Bacillus subtilisbiofilms contain TasA as major proteinaceous component in addition to exopolysaccharides. In stark contrast to the initially unfolded biofilm proteins of other bacteria, TasA is a soluble, stably folded monomer, whose structure we have determined by X-ray crystallography. Subsequently, we characterized in vitro different oligomeric forms of TasA by NMR, EM, X-ray diffraction, and analytical ultracentrifugation (AUC) experiments. However, by magic-angle spinning (MAS) NMR on live biofilms, a swift structural change toward only one of these forms, consisting of homogeneous and protease-resistant, β-sheet–rich fibrils, was observed in vivo. Thereby, we characterize a structural change from a globular state to a fibrillar form in a functional prokaryotic system on the molecular level.


1998 ◽  
Vol 71 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Leoncio Garrido

Abstract Silicone (polysiloxanes) gel-filled implants have been widely used for biomedical applications, mainly because they were considered to be nonbiodegradable. However, increasing concern about the health implications of polysiloxane exposure for women with silicone gel-filled breast implants has prompted interest to study the biochemistry of implanted polysiloxanes. The purpose of this work is to investigate the migration of polysiloxanes from the implant to local and distant sites and their chemical modification in living systems. Tissues from animals and humans exposed to polysiloxane gel implants are studied in vivo using proton NMR localized spectroscopy, and in vitro with proton and 29Si magic angle spinning (MAS) NMR spectroscopy. This work demonstrates that free polysiloxanes present in the gel-filled implants migrate to surrounding tissues and distant organs, such as the liver. In addition, 29Si NMR spectra of metabolically active tissues (liver) show the presence of chemically unchanged polysiloxanes and other silicon-containing compounds (silica) which suggest that these polymers are biodegradable.


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