Zhixiang Cai

Hyaluronan-Inorganic Nanohybrid Materials for Biomedical Applications

Nanomaterials, including gold, silver, and magnetic nanoparticles, carbon, and mesoporous materials, possess unique physiochemical and biological properties, thus offering promising applications in biomedicine, such as in drug delivery, biosensing, molecular imaging, and therapy. Recent advances in nanotechnology have improved the features and properties of nanomaterials. However, these nanomaterials are potentially cytotoxic and demonstrate a lack of cell-specific function. Thus, they have been functionalized with various polymers, especially polysaccharides, to reduce toxicity and improve biocompatibility and stability under physiological conditions. In particular, nanomaterials have been widely functionalized with hyaluronan (HA) to enhance their distribution in specific cells and tissues. This review highlights the most recent advances on HA-functionalized nanomaterials for biotechnological and biomedical applications, as nanocarriers in drug delivery, contrast agents in molecular imaging, and diagnostic agents in cancer therapy. A critical evaluation of barriers affecting the use of HA-functionalized nanomaterials is also discussed, and insights into the outlook of the field are explored.

Reduction- and pH-Sensitive Hyaluronan Nanoparticles for Delivery of Iridium(III) Anticancer Drugs

The organoiridium(III) complex (Ir(III)) [(η5-Cpxbiph)Ir(phpy) (py)]PF6 containing π-bonded biphenyltetramethylcyclopentadienyl(Cpxbiph), C∧N-chelated phenylpyridine(phpy), and pyridine (py) ligands has more potent antitumor activity as a new generation of drug than cisplatin toward various cancer cells. However, poor site-specific delivery, low solubility, and poor tumor penetration are common limitations of chemotherapy drugs. To develop CD44-targetable, pH-, and reduction-responsive drug delivery systems for Ir(III) drugs, the amphiphilic hyaluronan (HA)-based conjugates of HA-cystamin-pyrenyl (HA-ss-Py) containing disulfide bonds and HA-pyrenyl (HA-Py) were designed. The Ir(III) drug was readily loaded into these two amphiphilic conjugates and nanoparticles were formed. Dynamic light scattering (DLS) studies showed that the micelles formed from HA-ss-Py were sufficiently stable under physiological conditions, but were prone to rapid dissociation in reducing environments (20 mM glutathione (GSH)). In subsequent confocal microscopy analyses, A549 cancer cells efficiently internalized HA-based micelles. Moreover, in vitro cytotoxicity assays in A549 cells demonstrat that Ir-loaded HA-based nanoparticles have higher cytotoxicity than the free Ir(III) anticancer drug. Finally, systemic administration of Ir(III)-loaded HA-ss-Py nanoparticles enhanced tumor inhibition in vivo, and the corresponding biodistribution experiments showed that HA-ss-Py micelles accumulate in tumors. Overall, our results suggest that HA-ss-Py micelles have a great potential to be used as an effective Ir(III) drug carrier for targeted cancer therapy.