Original ArticleCoassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells
Graphical Abstract
The self-assembly of a peptide and a polysaccharide results in a nanostructured multifunctional scaffold that presents high density epitopes for healthy cell culture, while creating an anti-inflammatory environment to interrupt the cell cycle and induce apoptosis in cancer cells.
Section snippets
Methods
See Supplementary Information for full synthetic and analytical procedures.
The formation of two-component hydrogels and evaluation of (i) their biocompatibility and (ii) their effect on cancer cells
In order to form the scaffold to present fucoidan, we used a biocompatible minimalist pentapeptide sequence known to assemble via a π-β self-assembly mechanism, fluorenylmethoxycarbonyl (Fmoc) FRGDF (Figure 1).17, 18 Fmoc-FRGDF was synthesized using a standard solid phase Fmoc peptide synthesis methodology to yield a white crystalline powder (see electronic Supplementary Information). Fucoidan was supplied in a readily solubilized powder of similar consistency. We mixed both powders together
Discussion
The formation of stable, functional biomaterials that can present biologically active sequences and molecules will play a significant role in a range of medical applications. Self-assembly has been shown to give rise to materials that are both biocompatible and functional, but have not yet fully realized their potential. The use of simple interactions between these structures and additional functional molecules offers several advantages. The spontaneous formation of multicomponent scaffolds
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2022, Carbohydrate Polymer Technologies and ApplicationsCitation Excerpt :After flow cytometry, it was evidenced that the nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In another work, Li et al. (2016) exploited the anti-inflammatory activity of fucoidan to be used in cancer therapy, and it was demonstrated that the fucoidan contained in the nanogel inhibited cytokinesis and uncontrolled cell proliferation associated with tongue cancer. On their part, Shanmugapriya et al., (2019b) developed a nanogel containing chlorin e6, a second-generation photosensitizing agent which is stimulated to accumulate in tumors to absorb longer wavelengths more efficiently to destroy cancer cells.
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2022, Materials Today AdvancesCitation Excerpt :Initially, 5mg of the peptid was suspended in 400 μL MilliQ water (Milli-Q advantage A10 System, Merck Milipore, Melbourne, Australia). The suspension was then dissolved with a minimal volume (∼35 μL) of 0.5 M sodium hydroxide (NaOH), which has been shown to be effective and does not deprotect the Fmoc-from the peptide, as previously described [30,41,64,65] (Sigma-Aldrich Pty. Ltd, Sydney, Australia). The pH of the peptide solution was then slowly acidified by dropwise addition of 0.1 M hydrochloric acid (HCl) until a pH of 7.4 was reached (typically 30–60 μL).
A review on fucoidan antitumor strategies: From a biological active agent to a structural component of fucoidan-based systems
2020, Carbohydrate PolymersCitation Excerpt :Liposomes encapsulating fucoidan were also developed, inducing apoptosis of osteosarcoma cells and reducing tumor volume and weight in vivo, comparing to native fucoidan (Kimura, Rokkaku, Takeda, Senba, & Mori, 2013). In a different approach, fucoidan was added at the surface of a hydrogel (fluorenylmethoxycarbonyl) (Li et al., 2016). This self-assembly process was able to maintain fucoidan bioactivity, so that the scaffold provides a non-toxic environment for fibroblasts, although presenting toxicity to cancer cells.
This work was funded by an Australian Research Council (ARC) Discovery Project (DP130103131). N.M.R. instrumentation was provided through ARC funding (LE110100141). D.R.N. was supported by an NHMRC Career Development Fellowship (APP1050684). R.J.W. was supported via an Alfred Deakin Research Fellowship. Access to the facilities of the Centre for Advanced Microscopy (CAM) with funding through the Australian Microscopy and Microanalysis Research Facility (AMMRF) is gratefully acknowledged. A.J.C.D. was supported by the Swedish Research Council VR. Preliminary SANS measurements were performed at the Low Energy Neutron Source, Indiana. Access to the D33 instrument was provided by the Institut Laue-Langevin user access programme (8-03-826).
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D.R.N. and R.J.W. contributed equally to this work.