Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss.

BACKGROUND: Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive. METHODS: The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA. RESULTS: We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation. CONCLUSION: These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis.

GSK-3ß suppression upregulates Gli1 to alleviate osteogenesis inhibition in titanium nanoparticle-induced osteolysis.

Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3ß (GSK-3ß) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3ß phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3ß-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO.

Crosstalk Between the Neuroendocrine System and Bone Homeostasis.

The homeostasis of bone microenvironment is the foundation of bone health and comprises 2 concerted events: bone formation by osteoblasts and bone resorption by osteoclasts. In the early 21st century, leptin, an adipocytes-derived hormone, was found to affect bone homeostasis through hypothalamic relay and the sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine. This discovery has provided a new perspective regarding the synergistic effects of endocrine and nervous systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering the complex neuroendocrine regulation underlying bone homeostasis. Intriguingly, bone is also considered as an endocrine organ that can produce regulatory factors that in turn exert effects on neuroendocrine activities. After decades of exploration into bone regulation mechanisms, separate bioactive factors have been extensively investigated, whereas few studies have systematically shown a global view of bone homeostasis regulation. Therefore, we summarized the previously studied regulatory patterns from the nervous system and endocrine system to bone. This review will provide readers with a panoramic view of the intimate relationship between the neuroendocrine system and bone, compensating for the current understanding of the regulation patterns of bone homeostasis, and probably developing new therapeutic strategies for its related disorders.

MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3.

OBJECTIVES: The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. METHODS: The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. RESULTS: miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-ß1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. CONCLUSION: Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Comprehensive overview of microRNA function in rheumatoid arthritis.

MicroRNAs (miRNAs), a class of endogenous single-stranded short noncoding RNAs, have emerged as vital epigenetic regulators of both pathological and physiological processes in animals. They direct fundamental cellular pathways and processes by fine-tuning the expression of multiple genes at the posttranscriptional level. Growing evidence suggests that miRNAs are implicated in the onset and development of rheumatoid arthritis (RA). RA is a chronic inflammatory disease that mainly affects synovial joints. This common autoimmune disorder is characterized by a complex and multifaceted pathogenesis, and its morbidity, disability and mortality rates remain consistently high. More in-depth insights into the underlying mechanisms of RA are required to address unmet clinical needs and optimize treatment. Herein, we comprehensively review the deregulated miRNAs and impaired cellular functions in RA to shed light on several aspects of RA pathogenesis, with a focus on excessive inflammation, synovial hyperplasia and progressive joint damage. This review also provides promising targets for innovative therapies of RA. In addition, we discuss the regulatory roles and clinical potential of extracellular miRNAs in RA, highlighting their prospective applications as diagnostic and predictive biomarkers.

Theaflavin-3,3'-Digallate Ameliorates Collagen-Induced Arthritis Through Regulation of Autophagy and Macrophage Polarization.

Purpose: Previous studies have presented that theaflavin-3,3'-digallate (TFDG), one of natural flavonoids, have protective effects on collagen-induced arthritis (CIA). Besides, it was reported that TFDG could affect inflammatory signaling pathways, like NF-κB, JNK, and so on, to ameliorate inflammation. However, the anti-inflammatory mechanisms mentioned above are common to natural flavonoid products including TFDG. Therefore, this study aimed to further investigate the other mechanisms of TFDG against CIA. Methods: DBA/1 mice (8-10 weeks) were intravenously injected Freund's Adjuvant (100µL) at the base of tail and intraperitoneally injected PBS or different dosage of TFDG (1 mg/kg or 10 mg/kg). Then the paw and knee tissues were collected to assess the severity of joint destruction. In vitro experiments, bone marrow macrophages (BMMs) were exposed to TNF-α (10ng/mL) with or without different concentrations of TFDG (0.1µmol/L or 1.0µmol/L). Besides, the targets of TFDG were predicted with docking software and were verified through experiment. Results: TFDG treatment could reduce M1 macrophage (pro-inflammatory) and inflammatory cytokines, such as IL-1, IL- 6 and TNF-α, both in vitro and in vivo. At the same time, the M2 macrophage (alternatively activated) polarization was promoted by TFDG. Animal experiments showed TFDG ameliorated joint destructions. For investigating the mechanisms, the targets of TFDG were predicted by bioinformatics tools. According to predictions, we hypothesized that TFDG could act with BCL-2 to weaken the interaction between BCL-2 and Beclin1. Beclin1 plays a central role in autophagy, and we found that the autophagy level of BMMs was recovered by TFDG. Besides, 3-MA, an autophagy inhibitor, could attenuate the therapeutic effect of TFDG. Conclusion: TFDG protected against collagen-induced arthritis by attenuating the inflammation and promoting anti-inflammatory M2 macrophage polarization through controlling autophagy.

[Effects of the Crop Rotation on Greenhouse Gases from Flooded Paddy Fields].

A field experiment was conducted at the Key Field Station for Monitoring Eco-environment of Purple Soil of the Ministry of Agriculture of China in the farm of Southwest University, Chongqing. The static chamber and gas chromatography method was used to study the effect of the cropping systems on greenhouse gases from rice-fallow (RF), rice-rapeseed rotation (RR), and rice-brussel mustard rotation (RV) cropland in situ for a year. An opaque chamber was used for CH4 and N2O observations and a transparent chamber was utilized for CO2 observations. The results show that the annual cumulative CH4 emissions from different crop rotations were (CH4, kg·hm-2) RF (422.87±27.1) > RR (132.05±23.11) > RV (50.91±3.83). The RV and RR were significantly lower than RF (P<0.05). The annual cumulative emissions of N2O[N2O, kg·hm-2] were RV (21.38±6.51) > RR (20.02±5.23) > RF (0.48±0.02). The RV and RR were significantly higher than RF (P<0.05). The annual net cumulative emissions of CO2 were (CO2, t·hm-2) RR (-55.43±5.04) > RV (-29.1±3.00) > RF (-14.08±1.81). The RV and RR were significantly higher than RF (P<0.05). At the time scale of 100 a, the integrated global warming potentials (GWP) of CH4, N2O, and CO2 were (CO2, t·hm-2)RR(-46.43) > RV(-22.01) > RF(-2.11), indicating that converting flooded paddy fields to paddy-upland crop rotation systems notably increases the potential increment of carbon sinks. Compared with RV, RR has a better effect, which suggests that rice-rapeseed rotation is the most effective measure for the escalation of carbon sinks of ecosystems in the southwestern area.

Calorimetric lateral flow immunoassay detection platform based on the photothermal effect of gold nanocages with high sensitivity, specificity, and accuracy.

BACKGROUND: Lateral flow assays (LFA) play an increasingly important role in the rapid detection of various pathogens, pollutants, and toxins. PURPOSE: To overcome the drawbacks of low sensitivity and poor quantification in LFA, we developed a new calorimetric LFA (CLFA) using gold nanocages (GNCs) due to their high photothermal conversion efficiency, good stability of photophysical properties, and stronger penetrating ability of NIR light. METHODS: Thiol-polyethylene glycol-succinyl imide ester (HS-PEG-NHS) was modified onto GNCs, and the complex was conjugated with an antibody. Subsequently, the antibody-conjugated GNCs were analyzed by UV/Vis spectrophotometer, transmission electron microscope, high-resolution transmission electron microscope with energy dispersive spectrometer, dynamic light scattering instrument, and Atom force microscope. The GNC-based CLFA of alpha-fetoprotein (AFP) and zearalenone (ZEN), a food toxin, required nitrocellulose strips, a NIR laser source, and an infrared camera. RESULTS: The GNC-labeled CLFA platform technique exhibited detection sensitivity, qualitative specificity, and quantitative accuracy. The superior performance of the technique was evident both in sandwich format detection of biomacromolecules (eg, AFP protein) or competitive format detection of small molecules (eg, ZEN). After optimizing various test parameters, GNC-labeled CLFA provided ca. 5-6-fold enhanced sensitivity, higher correlativity (R 2>0.99), and more favorable recovery (82-115%) when compared with visual LFA. CONCLUSION: GNC-labeled CLFA may be a promising detection platform with high sensitivity, specificity, and precision.

Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization.

Transcatheter arterial embolization (TAE) plays an important role in clinical tumor therapy by accomplishing vessel-casting embolization of tumor arteries at all levels and suppressing tumor collateral circulation and vascular re-canalization. In this study, we describe smart blood-vessel-embolic nanogels for improving the anti-tumor efficacy of TAE therapy on hepatocellular carcinoma (HCC). Methods: In this study, an in vitro model composed of two microfluidic chips was used for simulating the tumor capillary network and analyzing artery-embolization properties. Also, blood-vessel-casting embolization of renal arteries was evaluated in normal rabbits. Using a VX2 tumor-bearing rabbit model, the therapeutic efficacy of TAE on HCC was investigated for tumor growth, necrosis, and proliferation. Neovascularization and collateral circulation were evaluated by immunofluorescent detection of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31 following the TAE therapy of VX2 tumor-bearing rabbits. Results: Sufficient embolization of all eight levels of micro-channels was achieved in a tumor-vessel-mimetic model with two microfluidic chips using PIBI-2240, and was further confirmed in renal arteries of normal rabbit. Effective inhibition of tumor collateral circulation and vascular re-canalization was observed in VX2 tumor-bearing rabbits due to the reduced expression levels of HIF-1α, VEGF, and CD31. Conclusions: The exceptional anti-tumor effect of PIBI-2240 observed in this study suggested that it is an excellent blood-vessel-embolic material for tumor TAE therapy.

Precise synchronization of hyperthermia-chemotherapy: photothermally induced on-demand release from injectable hydrogels of gold nanocages.

Though a therapeutic sequence plays a key role in tumor therapy, little attention has been paid to its influence on multimodal combined therapy. Herein, we developed gold nanocages (GNC@PNA-hls) decorated with two kinds of temperature sensitive p(N-isopropyl-acrylamide-acrylic acid) copolymers (PNA-hs and PNA-ls) for precise antitumor coordination of thermo-chemotherapy. Doxorubicin-loaded GNC@PNA-hls (Dox-GNC@PNA-hls) showed a steady photothermally induced on-demand release under multiple near-infrared (NIR) irradiations. In vitro evaluations indicated that concurrent thermo-chemotherapy treatments (Dox - L) showed the best antitumor effect, compared with the sequence of either doxorubicin treatment followed by NIR radiation (Dox + L) or NIR radiation followed by doxorubicin treatment (L + Dox). The in vivo antitumor efficacy also indicated that the tumor volume was totally suppressed (ca. 0.14 cm3) by the treatment of Dox-GNC@PNA-hls with NIR radiation for 14 days. These results indicated that Dox-GNC@PNA-hls could achieve precise synchronization between hyperthermia and chemotherapy, and effectively enhance their antitumor efficacy.

[Pollution Characteristics of Organic Carbon and Elemental Carbon in Atmospheric Aerosols in Beibei District, Chongqing].

To study the pollution characteristics of atmospheric carbon aerosols, aerosol samples were collected via a cascade impactor (Andersen) from March 2014 to February 2015 in Beibei District, Chongqing. Organic carbon (OC) and element carbon (EC) were detected using a DRI 2001A carbon analyzer. The results showed that the annual average concentrations of OC and EC in PM2.1 were (16.3±7.6) and (1.8±0.7), respectively, and (25.0±9.6), and (3.2±1.3) µg·m-3, respectively, in PM9.0. The concentrations of both OC and EC were higher in winter and spring than in summer and autumn for PM2.1, whereas, for PM9.0, the concentration of OC was higher in summer and spring than in winter and autumn and that of EC was higher in winter and spring than in summer and autumn. The particle size distributions of OC and EC for the study year were analyzed, and it was found that those of OC were bimodal, with peaks in the size ranges of 0.43-0.65 µm for fine particles and 4.7-5.8 µm for coarse particles, and those of EC were trimodal, with peaks in the size ranges of 0.43-0.65 µm for fine particles and 4.7-5.8 µm for coarse particles and a concurrent significant peak in the particle size range of 2.1-3.3 µm. In addition, the correlations between OC and EC were analyzed and the SOC in PM2.1 was estimated. It was found that the average concentration of SOC was (6.3±5.9) µg·m-3, which accounted for 33.5%±22.6% of the OC concentration in Beibei District. Furthermore, OC and EC were significantly correlated. Finally, the pollution sources of atmospheric aerosols in Beibei were analyzed, and it was found that the pollution in Beibei mainly came from the exhaust gas of gasoline vehicles, biomass combustion, and coal combustion.

Cisplatin-directed coordination-crosslinking nanogels with thermo/pH-sensitive triblock polymers: improvement on chemotherapic efficacy via sustained release and drug retention.

To realize the sustained release and long-term intratumoural retention of water-soluble cisplatin, thermo/pH-sensitive cisplatin-directed coordination-crosslinking nanogels (Pt-PNA) were developed via the coordination bonds of Pt-carboxyl groups. As the coordination ratio (CR) of the Pt-carboxyl bonds increased from 5% to 35%, the sizes of the Pt-PNA nanogels decreased from 999 nm to 167 nm, and their zeta potentials increased from -35 mV to -13 mV. Only through a simple mixing of cisplatin and PNAs, the entrapment efficiencies (EEs) of the Pt-PNA nanogels reached near 100% (>90%), and the drug-loading amounts (DLs) of cisplatin could achieve up to 25.5 ± 0.1%. For water-soluble cisplatin, Pt-PNA nanogels exhibited a sustained release for as long as 5 days. The thermo/pH-sensitive sol-gel phase-transition behaviour of the Pt-PNA nanogels were investigated via inverting-vial and rheological methods. Platinum elemental analysis indicated that the Pt-PNA nanogels showed a much stronger ability of cisplatin retention in tumours than free cisplatin. The platinum content in a tumour treated by the Pt-PNA nanogels was far higher than that by free cisplatin: 200.7 ± 63.6 µg vs. 82.7 ± 26.8 µg at the 1st day, or 118.9 ± 35.2 µg vs. 18.5 ± 9.4 µg at the 14th day. The evaluation of the in vivo antitumour efficacy indicated that only after a single dose of Pt-PNA nanogels, the tumour volume continuously decreased to 0.73 ± 0.07 times that of the original tumour volume (OTV) for 14 days; however, it rapidly increased by 3.37 ± 0.82, 8.01 ± 0.53 and 9.25 ± 1.85 times that of the OTV with the same dose of free cisplatin, PNA, and NS, respectively. Some preliminary evaluations of the biocompatibility indicated that the toxic side effects of cisplatin could be greatly improved via cisplatin-directed coordination-crosslinking with PNA. As a result, Pt-PNA nanogels could likely become a promising versatile strategy for improving antitumour efficacy and reducing the toxicity and size effects of platinum-based drugs, and they could also be developed as promising nanomedicines for regional chemotherapy.

Temperature sensitive p(N-isopropylacrylamide-co-acrylic acid) modified gold nanoparticles for trans-arterial embolization and angiography.

Temperature sensitive p(N-isopropylacrylamide-co-acrylic acid) modified gold nanoparticles (GNP@PNA) were prepared via coordination bonding between gold and sulfur elements. Their diameter and zeta potential were 86 nm and -26.2 mV at 25 °C, and 47 nm and -30.5 mV at 37 °C respectively. Thermogravimetric characterization of GNP@PNA indicated that the PNA shell and the GNP core accounted for 19.2 wt% and 78.2 wt%, namely ca. 70-80 chains of PNA were combined on the surface of one GNP nanoparticle. GNP@PNA showed much better X-ray attenuation ability, ca. 1.6-3.3 times higher than that of Omnipaque. In addition, the temperature sensitive sol-gel transition of GNP@PNA dispersions could realize the so-called "in situ casting" embolization from tumoral aorta to peripheral arteries, and improve their angiographic ability owing to the inhibition against GNP aggregation via gelation. Renal artery embolization on normal rabbits and TAE on VX2 tumor-bearing rabbits indicated that GNP@PNA achieved better embolization for longer times than Ivalon and Lipiodol. Excellent biocompatibility of GNP@PNA dispersions was also observed via the evaluation of cytotoxicity, hemolysis and hepatorenal function.

Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration.

Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature-sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1day, and 60% was released during 10days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13±0.04 times at 9days) and blank PNA100 (2.11±0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77±0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy.

The stimuli-responsive multiphase behavior of core-shell nanogels with opposite charges and their potential application in in situ gelling system.

Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol-gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol-gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core-shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to -0.33 and 0.082 mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9-2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0 wt%, 4-times lower than that of NIA and PND nanogels (about 8.0 wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system.

The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor.

Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions.