The traditional therapy of cancer has systemic side effects, and many cancers, such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumours. This study was aimed at enhancing the anti-tumour effect of curcumin (CUR) and preventing tumour spread to the bone. A novel multifunctional redox-responsive and CD44 receptor targeting polymer-drug, poly alendronate-hyaluronan-S-S-curcumin copolymer (ALN-oHA-S-S-CUR) based CUR and alendronate (ALN) were synthesized successfully with the disulphide bond linker. The structure of ALN-oHA-S-S-CUR was characterized by H-NMR. The nanomedicine had natural anti-tumour drugs (CUR) as the hydrophobic kernel, and targeting CD44 receptor oligosaccharides of hyaluronan (oHA) and other anti-tumour drugs (ALN) as hydrophilic shell, named ALN-oHA-S-S-CUR conjugates, which could self-assemble into micelle-like nano-spheres in water via a dialysis method with hydrodynamic diameters of 179 ± 23 nm. Interestingly, the cur-loaded ALN-oHA-S-S-CUR micelles were stable in PBS but were capable of releasing the drug under the reducing environment. The rate of drug release was proportional to the GSH concentration. The uptake and cytotoxicity of micelles were higher in MDA-MB-231 cells than in MCF-7 cells because of a higher expression of the CD44 receptor in the former cell line. And compared to the cur-loaded oHA-CUR micelles, the cur-loaded ALN-oHA-S-S-CUR micelles had a good cellular uptake in 2D cancer cell and penetrability in 3D cancer cell spheroids. These results indicated the active targeting redox-sensitive micelles were promising as intracellular drug delivery systems for cancer treatment.
Summary
Cyanobacteria, a phylum of bacteria that obtains energy by oxygenic photosynthesis, can be found in almost every terrestrial and aquatic habitat on Earth and play an important role in global carbon and oxygen cycles and as food sources for fish. However, common bloom‐forming cyanobacteria in the genus Microcystis produce microcystins that are toxic to human beings and aquatic animals and can have disastrous effects in aquatic ecosystems.
Algal species follow seasonal successions of bloom formation and Microcystis spp. have been reported to be more competitive than other algal species in lakes. However, so far there has been no clear demonstration of competition among Microcystis species.
By means of growth experiments, we demonstrate that two common cyanobacterial species Microcystis aeruginosa FACHB‐905 and Microcystis flos‐aquae FACHB‐1028, which are the dominant toxigenic species in Lake Taihu, exhibit a competitive relationship under coculture condition, the former outcompeting the latter.
We show that M. aeruginosa is a superior competitor to M. flos‐aquae regardless of temperature, nutrients and initial abundance ratios. Moreover, both unicultured filtrates of M. aeruginosa and cocultured filtrates of both species strongly inhibit the growth of M. flos‐aquae.
An analysis using gas chromatography mass spectrometry of extracts of filtrates from unicultures and cocultures indicates that some extracellular allelopathic compounds produced by M. aeruginosa, such as D‐limonene and 1‐chlorine heptacosane, might play important roles in competition among the species.
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