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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 1H-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. [ABSTRACT FROM AUTHOR]

To remedy the problems resulting from the usage of anti-cancer drugs in cancer chemotherapy, such as deficient drug concentration in tumour cells, low water-solubility and non-specific distribution of antitumour drugs, a kind of reduction-sensitive polymer prodrug of curcumin (Cur) containing in the nano-echinus was synthesized and designed. The nano-echinus-like nanomedicine presented synergistic effect with glycyrrhetic acid (GA) and oligomeric hyaluronic (HA) for targeting and combating HepG2 human liver cancer cell. Firstly, a kind of small molecular prodrug of Cur, dithiodipropionic acid-Cur (-SS-Cur), was chemically conjugated onto the side chain of the conjugated glycyrrhetic acid- oligomeric hyaluronic (GA-HA) to generate an amphiphilic polymeric prodrug of Cur, GA-HA-SS-Cur. The obtained GA-HA-SS-Cur prodrug and subsidiary material mPEG-DSPE could self-assemble into a sea urchin-like micelles in aqueous media and release Cur rapidly in response to glutathion (GSH). Then, Cur was loaded into the nano-echinus with a particle size of (118.1 ± 0.2 nm) and drug-loading efficiency of (8.03 ± 2.1%). The structure of GA-HA-SS-Cur was characterized by 1H-NMR in this report. The morphology of micelles was observed with a transmission electron microscope (TEM). Subsequently, the reduction-sensitivity of the nano-echinus was confirmed by the changes in in-vitro drug release after different concentrations of GSH treatment. Besides, the cellular uptake behaviour and MTT assays of the nano-echinus were investigated, suggesting that the nano-echinus was of desirable safety and could be taken into HepG2 cells in a time-dependent manner. Later, anti-tumour efficacy in vivo revealed the effective inhibition of tumour growth. [ABSTRACT FROM AUTHOR]