Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe 3 O 4 ) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe 3 O 4 were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe 3 O 4 particles were then conjugated with Bis to form Bis/Dex/Fe 3 O 4 . Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe 3 O 4 particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe 3 O 4 by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe 3 O 4 and Bis/Dex/Fe 3 O 4 nanoparticles possessed their respective Dex and Bis functional groups, while a superconducting quantum interference device magnetometer measured the magnetic moment to be 24.5 emu. In addition, the Bis/Dex/Fe 3 O 4 nanoparticles were fully dispersed in double-distilled water. Osteoblasts and OCs were individually cultured with the nanoparticles, and an MTT assay revealed that they were non-cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles for 20 minutes, and the thermal effect was found to be sufficient to destroy OCs. Furthermore, in vivo studies verified that nanoparticles were indeed magnetic resonance imaging contrast agents and that they accumulated after being injected into the body of rats. In conclusion, we developed a water-dispersible magnetic nanoparticle that had RF-induced thermogenic properties, and the results indicated that the Bis/Dex/Fe 3 O 4 nanoparticle had the potential for controlling osteoporosis.

Biocompatible and temperature-sensitive amphiphilic polymeric micelles comprised of poly(succinimide)-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PSI-g-poly(NIPAAm-co-DMAAm)) were synthesized to use as new drug carriers. The PSI-co-poly(PNIPAAm-co-DMAAm) polymers were prepared by nucleophilic opening of poly(succinimide) using amino-terminated poly(NIPAAm-co-DMAAm). The lower critical solution temperature of the copolymer was 40.6℃ higher than normal human body temperature. The blank polymeric micelles were observed to have a regular spherical shape, and the particle sizes were approximately 85 nm. This copolymer exhibited no significant cytotoxicity and hemolysis indicated that the micelles had good biocompatibility. In addition, these polymeric micelles encapsulated the anti-inflammatory drug, hesperetin, in the inner core with a drug loading content of approximately 20%. The release profiles of hesperetin showed a significant temperature-sensitive switching behavior. The hesperetin release response was dramatically lower at a temperature below the lower critical solution temperature as compared with a temperature above the lower critical solution temperature. The lipopolysaccharide-induced nitric oxide production inhibition experiments demonstrated that hesperetin-encapsulated micelles showed a significant reduction. In this study, the biocompatible temperature-sensitive micelles based on PSI-g-poly(NIPAAm-co-DMAAm) have great potential to act as a suitable carrier for drug delivery.

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The multi-functional micelles poly( N -isopropylacrylamide- co - N , N -dimethylacrylamide- co -10 undecanoic acid)/CM-Dextran Fe 3 O 4 (PNDU/CM-Dex Fe 3 O 4 ) were poly (NIPAAm- co -DMAAm- co -UA) (PNDU) grafting hydrophilic CM-Dextran Fe 3 O 4 which possess pH-dependent temperature response and magnetic response. In this research, anti-inflammation drug Hesperetin was encapsulated by micelles using membrane dialysis method to obtain the different ratio of Hesperetin-embedded P 5 DF 10 , P 10 DF 10 , and P 20 DF 10 . These micelles were characterized by Fourier transform infrared spectroscopy, 1 H-NMR, thermogravimetric analyzer, and superconducting quantum interference device magnetometer. The morphology and particle size of micelles was observed by transmission electron microscopy and dynamic light scattering. The low critical solution temperature of the P 10 DF 10 micelles is in pH 6.6 at about 37.76°C and in pH 7.4 at about 41.70°C. The biocompatibility of micelles was confirmed by cytotoxicity study. Inflammatory inhibition of hesperetin-embedded P 10 DF 10 micelles also studied through RAW264.7. Hesperetin-embed P 10 DF 10 micelles suppressed LPS-induced inflammatory response. Via immunofluorescence cell staining demonstrate that Hesperetin-embed P 10 DF 10 micelles inhibited the activation of NF-κB p60 and markedly attenuated in a drug dose-dependent manner. At a concentration of 1,000 ug/ml, an inflammatory rate can be reduced to 36.9%. Based on these results, the hesperetin-embed P 10 DF 10 micelles had successfully synthesized and enable to carry and release the anti-inflammatory drugs, which instrumental for biomedical therapy and applications.