Multifunctional redox-responsive and CD44 receptor targeting polymer-drug nanomedicine based curcumin and alendronate: synthesis, characterization and in vitro evaluation

Abstract

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.

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…Multifunctional redox-responsive and CD44 receptor targeting polymer-drug nanomedicine Targeted drug delivery with enhanced anti-tumor efficacy [350] Iridium(III) anticancer drugs…”

Synthesis, characterization and in vitro/in vivo evaluation of novel reduction-sensitive hybrid nano-echinus-like nanomedicine

“…Then, with the CD44 targeting ability of HA to the nano-echinus could target to CD44-receptors on the surface of tumour cells and accumulate in tumour tissues [18]. Finally, with the aid of the disulfide bond as the reductionsensitive linker, the Cur can be released in tumour environments [19]. Meanwhile, with the existence of mPEG, the circulating time of drug carriers could be prolonged [2].…”

Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs

“…The disulphide bond was a connection arm of the conjugate, and it enhanced the drug loading and encapsulation efficiency of curcumin. It also promoted tumor targeting of the conjugate [103].…”

“…Dong et al successfully prepared oligosaccharides of hyaluronan (hydrophilic polysaccharide)based polymer-drug conjugates incorporated with curcumin and alendronate via disulphide linker [103]. Proton Nuclear Magnetic Resonance Spectroscopy ( 1 HNMR) was employed to confirm the physiochemical structure of the conjugates.…”