Chunqiu Zhao

Recent advances in nano scaffolds for bone repair

Biomedical applications of nanomaterials are exponentially increasing every year due to analogy to various cell receptors, ligands, structural proteins, and genetic materials (that is, DNA). In bone tissue, nanoscale materials can provide scaffold for excellent tissue repair via mechanical stimulation, releasing of various loaded drugs and mediators, 3D scaffold for cell growth and differentiation of bone marrow stem cells to osteocytes. This review will therefore highlight recent advancements on tissue and nanoscale materials interaction.

In Situ Biosynthesis of Fluorescent Platinum Nanoclusters: Toward Self-Bioimaging-Guided Cancer Theranostics

Among the noble-metal clusters, very few reports about platinum clusters were used as bioimaging probes of tumors except as a reducing catalyst. It is first established herein that the biocompatible platinum nanoclusters are spontaneously biosynthesized by cancerous cells (i.e., HepG2 (human hepatocarcinoma), A549 (lung cancer), and others) rather than noncancerous cells (i.e., L02 (human embryo liver cells)) when incubated with micromolar chloroplatinic acid solutions. These in situ biosynthesized platinum nanoclusters could be readily realized in a biological environment and emit a bright fluorescence at 460 nm, which could be further utilized to facilitate an excellent cancer-cell-killing efficiency when combined with porphyrin derivatives for photothermal treatment. This raises the possibility of providing a promising and precise bioimaging strategy for specific fluorescent self-biomarking of tumor locations and realizing fluorescence imaging-guided photothermal therapy of tumors.

Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics

Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-α level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint.

Rapid and multimodal in vivo bioimaging of cancer cells through in situ biosynthesis of Zn&Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment, and hence, there is significant interest in the development of effective imaging strategies. This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e., HeLa, U87, and HepG2 cancer cells). We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters. These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging. Meanwhile, for normal cells (i.e., L02) and tissues, neither fluorescence nor any other obvious difference could be detected between preand post-injection. This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.

Biosynthesized Gold Nanoclusters and Iron Complexes as Scaffolds for Multimodal Cancer Bioimaging.

Cancer treatment has a far greater chance of success if the neoplasm is diagnosed before the onset of metastasis to vital organs. Hence, cancer early diagnosis is extremely important and remains a major challenge in modern therapeutics. In this contribution, facile and new method for rapid multimodal tumor bioimaging is reported by using biosynthesized iron complexes and gold nanoclusters via simple introduction of AuCl4- and Fe2+ ions. The observations demonstrate that the biosynthesized Au nanoclusters may act as fluorescent and computed tomography probes for cancer bioimaging while the iron complexes behave as effective contrast agent for magnetic resonance imaging. The biosynthesized iron complexes and gold nanoclusters are found biocompatible in vitro (MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay) and in vivo for all the vital organs of circulatory and excretory system. These observations raise the possibility that the biosynthesized probes may find applications in future clinical diagnosis for deep seated early neoplasms by multimodal imaging.

Fluorescent gold nanoclusters for in vivo target imaging of Alzheimer's disease

Alzheimers disease involves the formation of numerous senile plaques (SPs) composed of β-amyloid (Aβ) peptides. At the same time the level of various redox-active metal ions changes leading to a completely different redox environment in the brains of Alzheimers patients compared with the normal brain. Given these considerations, we have explored a new strategy of in vivo rapid fluorescence bio-imaging of Alzheimers disease through target bio-labeling of the diseased sites. The sites are exposed to aqueous solutions of chloroauric acid (HAuCl4), which subsequently forms Au salts. These salts then self-assemble into gold nanoclusters (Au NCs), which can then be used for fluorescence imaging. For instance, taking Alzheimers model mice (AD) and a normal control group of mice (NOR) as models, our studies demonstrate that intravenous injection of aqueous HAuCl4 through the AD mice tails allowed accurate bright fluorescence labeling around the affected sites of the Alzheimers brain within a couple of hours, while this did not occur in normal mice (controls): the control mice did not exhibit any fluorescent areas even 24 h after intravenous injection of an identical or larger amount of aqueous HAuCl4. These observations suggest that HAuCl4 molecules could readily pass through the blood–brain barrier (BBB) of the AD mice and then mainly accumulate on the hippocampus specific region, followed by in situ biosynthesis of the Au NCs for fluorescent labeling of the affected sites of the Alzheimers brain. This strategy provides a new method for the rapid and early diagnosis of Alzheimers disease and may have potential for effective theranostics of Alzheimers disease.

Protective effect of TiO2 nanowhiskers on Tetra Sulphonatophenyl Porphyrin (TSPP) complexes induced oxidative stress during photodynamic therapy.

BACKGROUND Tetra Sulphonatophenyl Porphyrin (TSPP) is well known photosensitizer for photodynamic therapy; nevertheless, its well-known adverse effects hamper its potential use. Recently, nano TiO2s potential role in biomedical has been defined for various disease theranostics, including cancer and other infections. Thus, in this contribution we have explored the possibility of utilizing TiO2 nanowhiskers as novel strategy to lower TSPP adverse effects both in vitro, and in vivo. METHODS Various concentrations of TSPP, TiO2-TSPP, and TiO2 were injected to three different rat groups, while fourth group was kept as control. Toxic effects were evaluated on excretory and circulatory system by using histopathology, fluorescent microscopy, complete blood cells count (CBC) and serum enzymes. RESULTS In complete blood cells count, all cells were significantly (p<0.01) affected by the various concentration and treatment groups. The various dose concentrations and treatment also significantly (p<0.01) affected the serum enzyme parameters including AST, ALT, LDH, Creatinine and BUN level. The low concentration of TSPP-TiO2 was found to be the safest, on the bases of serum enzyme parameters, CBC, histopathology, and fluorescent microscopic analysis. The MTT assay was used to evaluate in vitro cytotoxicity, and the results demonstrated maximum viability in illuminated TSPP-TiO2 nanowhiskers group when compared with TSPP treated group. CONCLUSIONS It was evident that increase in concentration of TSPP increased the toxic effects; however, the TiO2 nanowhiskers combination with TSPP decreased these adverse effects. Moreover, TSPP (0.1 mM) combined with TiO2 nanowhiskers (0.6 mM) was safer than TSPP (0.1 mM) alone.

Titanium dioxide-tetra sulphonatophenyl porphyrin nanocomposites for target cellular bio-imaging and treatment of rheumatoid arthritis

Photodynamic therapy (PDT) is one of the latest biomedical technologies used for treatment of various neoplastic and non-neoplastic diseases. However, there still exist some well-known problems regarding its efficacy, e.g. effective concentration of the drug at the desired sites, the irradiation light dosimetry and biocompatibility of the photosensitizer. The introduction of nanotechnology and nanomaterial like biocompatible nano-titania (i.e., nano-TiO2) may facilitate to solve some of these problems. In this study we have explored the possibility of combining tetra sulphonatophenyl porphyrin (TSPP) with nano-titania (PT) for efficient PDT with least adverse effects. The spectroscopic properties of these nano-composites were characterized by using fluorescence and UV-Vis absorption spectroscopic study. The singlet oxygen quantum yield was determined by using 2,5-diphenyl-3,4-benzofuran (DPBF), while the effect of nano TiO2 with TSPP on the synovial fibroblast cells from human (HSC) and rat models (RSC) were investigated by confocal laser microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Our results suggest that nano TiO2 with TSPP can be readily utilized for effective PDT treatment of Rheumatoid Arthritis (RA).

Novel conjugated Ag@PNIPAM nanocomposites for an effective antibacterial wound dressing

It is well known that nanosilver or silver ions could act as an effective antibacterial agent without the development of bacterial resistance but long term exposure may induce in vivo toxicity. Thus, specific care should be taken before relevant silver-containing materials are used as antibacterial agents. Recently biocompatible polymeric materials are widely used to reduce the toxic effects of nanomaterials, which could be utilized to fabricate antibacterial surface coatings with good biocompatibility. In this study we have developed a simple and green synthesis strategy to prepare Ag@PNIPAM nanocomposites with high purity and good bioactivity for promising bio-applications as highly effective antimicrobial agents. The relevant synthesis takes place in a clean environment without any chemical additives, which ensures ultrahigh active surfaces of the Ag clusters. The as-prepared Ag@PNIPAM nanocomposites exhibit highly effective antimicrobial activities against Staphylococcus aureus (S. aureus) and have a good therapeutic effect for burn wounds.

Synergy and translation of allogenic bone marrow stem cells after photodynamic treatment of rheumatoid arthritis with tetra sulfonatophenyl porphyrin and TiO2 nanowhiskers

Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin (TSPP) and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly (p < 0.01) lower the concentrations of serum biomarkers (tumor necrosis factor-α and interleukin-17) in a collagen induced arthritis (CIA) murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rno-mir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.