AIE Supramolecular Assembly with FRET Effect for Visualizing Drug Delivery.

Here, we constructed a nanostructured pH/redox dual-responsive supramolecular drug carrier with both aggregation-induced emission (AIE) and Forster resonance energy transfer (FRET) effects, which enabled selective drug release and monitoring drug delivery and release processes. Taking the hyperbranched polyamide amine (H-PAMAM) with intrinsic AIE effects as the core, poly(ethylene glycol) (PEG) was bridged on its periphery by dithiodipropionic acid. Then, through the host-guest interaction of PEG and α-cyclodextrin, the supramolecular nanoparticles with AIE effects were constructed to load the anticancer drug doxorubicin (DOX). The supramolecular assembly has sufficiently large DOX loading due to the abundant cavities formed by branched structures. The hyperbranched core H-PAMAM has strong fluorescence, and the dynamic track of drug carriers and the dynamic drug release process can be monitored by the AIE and FRET effects between H-PAMAM and DOX, respectively. Furthermore, the introduction of disulfide bonds and the pH sensitivity of H-PAMAM enable the achievement of rapid selective release of loaded DOX at the tumor while remaining stable under normal physiological conditions. In vitro cytotoxicity indicates that the drug-loaded supramolecular assembly has a good therapeutic effect on cancer. In addition, the H-PAMAM core is different from the traditional AIE functional group, which has no conjugated structure, such as a benzene ring, thereby providing better biocompatibility. This technology will have broad applications as a new drug delivery system.

The design strategy of intelligent biomedical magnesium with controlled-release platform.

Magnesium has a very promising adhibition in biomedical field for its excellent mechanical and biodegradable properties, however, the intelligent applications of biomedical magnesium developed difficultly due to its characteristic degradation. A intelligent biomedical magnesium was constructed on magnesium (Mg) surface by incorporating polydopamine (PD) and mechanized hollow mesoporous silica nanoparticles (HMSs) as smart delivery platform nanocontainers. The supramolecular nanovalves of mechanized HMSs consisted of alginate/chitosan multilayers by self-assembly, which are capable of entrapping rhodamine 6G in the mesopores and can release the cargo under the chemical environment of alkali or Mg iron stimuli that correspond to the degradation of biomedical Mg. The alkali/Mg2+ dual stimuli-responsive release property of the HMSs endows the biodegradable Mg with controlled release potential. The well-designed smart delivery nanocontainers were combined with polydopamine deposited on Mg for excellent adhesion properties and positively charged amino group of PD. Furthermore, when the biomedical Mg with these mechanized HMSs was degraded in the simulated body environment, the alkali/Mg2+-triggered release of cargos from this smart delivery platform could bring a more functional application.

Biodegradation behavior of magnesium and ZK60 alloy in artificial urine and rat models.

In this work, the biodegradable and histocompatibility properties of pure Mg and ZK60 alloy were investigated as new temporary implants for urinary applications. The corrosion mechanism in artificial urine was proposed using electrochemical impedance spectroscopy and potentiodynamic polarization tests. The corrosion potential of pure magnesium and ZK60 alloy were -1820 and -1561 mV, respectively, and the corrosion current densities were 59.66 ± 6.41 and 41.94 ± 0.53 µA cm-2, respectively. The in vitro degradation rates for pure Mg and ZK60 alloy in artificial urine were 0.382 and 1.023 mm/y, respectively, determined from immersion tests. The ZK60 alloy degraded faster than the pure Mg in both artificial urine and in rat bladders (the implants of both samples are ø 3 mm × 5 mm). Histocompatibility evaluations showed good histocompatibility for the pure Mg and ZK60 alloy during the 3 weeks post-implantation in rat bladders, and no harm was observed in the bladder, liver and kidney tissues. The results provide key information on the degradation properties and corrosion mechanism of pure Mg and ZK60 alloy in the urinary system.

In vitro and in vivo corrosion and histocompatibility of pure Mg and a Mg-6Zn alloy as urinary implants in rat model.

Pure Mg and a Mg-6wt.% Zn alloy were investigated as potential candidates for biodegradable implants for the urinary system. The in vitro corrosion behavior was studied by potentiodynamic polarization and immersion tests in simulated body fluid (SBF) at 37°C. The in vivo degradation and histocompatibility were examined through implantation into the bladders of Wistar rats. The alloying element Zn elevated the passivation potential and increased the cathodic current density. Both in vitro and in vivo degradation tests showed a faster corrosion rate for the Mg-6Zn alloy. Tissues stained with hematoxylin and eosin (HE) suggested that both pure Mg and Mg-6Zn alloy exhibited good histocompatibility in the bladder indwelling implantation and no differences between pure Mg and Mg-6Zn groups were found in bladder, liver and kidney tissues during the 2weeks implantation. Overall, this work presented instructive information on the degradation properties and histocompatibility of pure Mg and the Mg-6Zn alloy in the urinary system.

Effects of gas produced by degradation of Mg-Zn-Zr Alloy on cancellous bone tissue.

Mg-Zn-Zr alloy cylinders were implanted into the femoral condyles of Japanese big-ear white rabbits. X-ray showed that by 12 weeks following implantation the implant became obscure, around which the low-density area appeared and enlarged. By 24 weeks, the implant was more obscure and the density of the surrounding cancellous bone increased. Scanning electron microscopy examination showed bone tissue on the surface of the alloy attached by living fibers at 12 weeks. Micro-CT confirmed that new bone tissue on the surface of the residual alloy implant increased from 12 weeks to 24 weeks. By 12 weeks, many cavities in the cancellous bone tissue around the implant were noted with a CT value, similar to gas value, and increasing by 24 weeks (P<0.01). Histological examination of hard tissue slices showed that bone tissue was visibly attached to the alloy in the femoral condyle at 12 weeks. The trabecular bone tissues became more intact and dense, and the cavities were filled with soft tissue at 24 weeks. In general, gas produced by the degradation of the Mg-Zn-Zr alloy can cause cavitation within cancellous bone, which does not affect osteogenesis of Mg alloy.

In vivo comparative property study of the bioactivity of coated Mg-3Zn-0.8Zr alloy.

In this in vivo study, degradable Mg-3Zn-0.8Zr cylinders were coated with a calcium phosphorus compound (Ca-P) layer or a magnesium fluoride (MgF2) layer; uncoated Mg-3Zn-0.8Zr alloy was used as a control. These were then implanted intramedullary into the femora of nine Japanese big-ear white rabbits for implantation periods of 1, 2 and 3 months. During the postoperative observation period with radiographic examination, the results showed that the MgF2-coated implants were tolerated well compared to the Ca-P-coated implants and uncoated implants. Moreover, large amounts of cells, rich fibrillar collagen and calcium and phosphorus products were found on the surface of the MgF2-coated implants using scanning electron microscopy. Micro-computed tomography further showed a slight decrease in volume (23.85%) and a greater increase in new bone mass (new bone volume fraction=11.56%, tissue mineral density=248.81 mg/cm(3)) for the MgF2-coated implants in comparison to uncoated and Ca-P compound-coated implants after 3 months of implantation.