Dataset Information

Development of photoactive Sweet-C₆₀ for pancreatic cancer stellate cell therapy.

ABSTRACT:

Aim

Glycoconjugated C₆₀ derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells.

Materials & methods

Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C₆₀ derivative (termed 'Sweet-C₆₀').

Results

Synthesized fullerene derivative predominantly accumulates in the nucleus of pancreatic stellate cells; is inherently nontoxic up to concentrations of 1 mg/ml; and is photoactive when illuminated with blue and green light, allowing its use as a photodynamic therapy agent.

Conclusion

Obtained glycoconjugated nanoplatform is a promising nanotherapeutic for pancreatic cancer.

SUBMITTER: Serda M

PROVIDER: S-EPMC6462851 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of photoactive Sweet-C<sub>60</sub> for pancreatic cancer stellate cell therapy.

Serda Maciej M Ware Matthew J MJ Newton Jared M JM Sachdeva Sanchit S Krzykawska-Serda Martyna M Nguyen Lam L Law Justin J Anderson Andrew O AO Curley Steven A SA Wilson Lon J LJ Corr Stuart J SJ

Nanomedicine (London, England) 20181203 23

<h4>Aim</h4>Glycoconjugated C<sub>60</sub> derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells.<h4>Materials & methods</h4>Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C<sub>60</sub> derivative (termed 'Sweet-C<sub>60</sub>').<h4>Results</ ...[more]

PMID: 30501557

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Project description:A photostable and photodynamic antimicrobial surface was successfully obtained and applied to photoinactivate microorganisms. This approach was based on the synthesis of a fullerene C60 derivative (EDOT-C60) where fullerene C60 is covalently linked to 3,4-ethylenedioxythiophene (EDOT) through a 1,3-dipolar cycloaddition reaction. This dual-functional monomer bears an EDOT center connected via an alkyl chain to a fullerene C60 moiety. In this structure, EDOT acts as an electropolymerizable unit that allows the film formation over conducting substrates, while fullerene C60 performs the photodynamic antimicrobial activity. Electrochemical polymerization of EDOT was used to obtain stable and photodynamic polymeric films (PEDOT-C60) in a controllable procedure. Cyclic voltammetry and UV-visible spectroscopy studies showed that the fullerene C60 units were not altered during the electropolymerization process, obtaining surfaces with high fullerene content. Photobleaching measurements demonstrated that the electropolymerized films were highly photostable. Moreover, photodynamic properties of PEDOT-C60 were compared with fullerene C60 and showed that electrodeposited films were able to generate reactive oxygen species (ROS) through the two photomechanisms, producing singlet molecular oxygen (type II) and superoxide radical anion (type I). All studies demonstrated that fullerene C60 moieties covalently attached to the polymeric matrix mainly conserve the photodynamic characteristics. Hence, photodynamic action sensitized by PEDOT-C60 was assessed in vitro against Staphylococcus aureus. The photosensitized inactivation by the electropolymerized films on bacteria suspensions produced >99.9% reduction in S. aureus survival. Fluorescence microscopy experiments with S. aureus adhered to the PEDOT-C60 surface showed a complete microbe annihilation. Also, the eradication of biofilms formed on PEDOT-C60 surfaces resulted in a photokilling >99.9% after visible light irradiation. Our results demonstrated that these antimicrobial photodynamic polymeric films are a promising and versatile platform to photoinactivate microorganisms and to obtain photostable self-sterilizing surfaces.

Project description:Pancreatic cancer is characterized by a hypoxic tumor microenvironment, which is primarily caused by massive fibrosis with pancreatic stellate cells (PSCs) as a main component. Our previous studies have shown that resveratrol can significantly inhibit pancreatic cancer. However, whether resveratrol can inhibit hypoxia-induced cancer development remains unclear. The objective of this study was to explore whether PSCs and hypoxia synergistically mediate aggressiveness in pancreatic cancer and detect the potential pleiotropic protective effects of resveratrol on hypoxia-induced pancreatic cancer progression. Human PSCs were treated with vehicle or resveratrol under normoxic or hypoxic conditions (3% O2), and PSC activation was assessed by immunofluorescence staining. SiRNA was used to silence hypoxia-inducible factor 1 (HIF-1) expression. The invasive capacity of Panc-1 and Mia Paca-2 cells cocultured with conditioned medium from PSCs was assessed by Transwell assays. To examine tumor formation kinetics, KPC (LSL-KrasG12D/+, Trp53fl/+, and Pdx1-Cre) mice were sacrificed at different time points. To investigate the antitumor effects of resveratrol in vivo, 8-wk-old KPC mice were divided into two groups and treated daily with or without 50 mg/kg resveratrol. Our data indicate that hypoxia induces PSC activation via HIF-1 and that the interleukin 6, vascular endothelial growth factor A, and stromal cell-derived factor 1 derived from activated PSCs promote both invasion and the epithelial-mesenchymal transition and inhibit apoptosis in pancreatic cancer cells. However, resveratrol inhibits hypoxia-induced PSC activation, blocks the interplay between PSCs and pancreatic cancer cells, and suppresses the malignant progression of pancreatic cancer and stromal desmoplasia in a KPC mouse model. Our data highlight that activated PSCs and intratumoral hypoxia are essential targets for novel strategies to prevent tumor-microenvironment interactions. Furthermore, the polyphenolic compound resveratrol effectively ameliorates the malignant progression of pancreatic ductal adenocarcinoma.

Dataset Information

Development of photoactive Sweet-C₆₀ for pancreatic cancer stellate cell therapy.

Aim

Materials & methods

Results

Conclusion

Publications

Development of photoactive Sweet-C<sub>60</sub> for pancreatic cancer stellate cell therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Development of photoactive Sweet-C60 for pancreatic cancer stellate cell therapy.

Aim

Materials & methods

Results

Conclusion

Publications

Development of photoactive Sweet-C<sub>60</sub> for pancreatic cancer stellate cell therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Development of photoactive Sweet-C₆₀ for pancreatic cancer stellate cell therapy.