Daxiang Cui

Light-Triggered Theranostics Based on Photosensitizer-Conjugated Carbon Dots for Simultaneous Enhanced-Fluorescence Imaging and Photodynamic Therapy

National Key Basic Research Program (973 Project) [2010CB933901, 2011CB933100]; National Natural Scientific Fund [51102258, 20803040, 81028009, 31170961]; New Century Excellent Talent of Ministry of Education of China [NCET-08-0350]; Shanghai Science and Technology Fund [1052nm04100]; Ministry of Education

Photosensitizer-Loaded Gold Vesicles with Strong Plasmonic Coupling Effect for Imaging-Guided Photothermal/Photodynamic Therapy

A multifunctional theranostic platform based on photosensitizer-loaded plasmonic vesicular assemblies of gold nanoparticles (GNPs) is developed for effective cancer imaging and treatment. The gold vesicles (GVs) composed of a monolayer of assembled GNPs show strong absorbance in the near-infrared (NIR) range of 650-800 nm, as a result of the plasmonic coupling effect between neighboring GNPs in the vesicular membranes. The strong NIR absorption and the capability of encapsulating photosensitizer Ce6 in GVs enable trimodality NIR fluorescence/thermal/photoacoustic imaging-guided synergistic photothermal/photodynamic therapy (PTT/PDT) with improved efficacy. The Ce6-loaded GVs (GV-Ce6) have the following characteristics: (i) high Ce6 loading efficiency (up to ~18.4 wt %; (ii) enhanced cellular uptake efficiency of Ce6; (iii) simultaneous trimodality NIR fluorescence/thermal/photoacoustic imaging; (iv) synergistic PTT/PDT treatment with improved efficacy using single wavelength continuous wave laser irradiation.

RGD-Conjugated Dendrimer-Modified Gold Nanorods for in Vivo Tumor Targeting and Photothermal Therapy†

Successful development of safe and effective nanoprobes for tumor targeting and selective therapy is a challenging task. Although gold nanorods(GNRs) have the potential to perform such a role, the toxicity of surfactant cetyltrimethylammonium bromides (CTAB) on their surfaces limits their applications. Here, polyamidoamine dendrimer was applied to replace CTAB molecules on the surface of gold nanorods. When the resultant dendrimer-modified gold nanorods conjugated with arginine-glycine-aspartic acid (RGD) peptides, they showed highly selective targeting and destructive effects on the cancer cells and solid tumors under near-infrared laser irradiation. Also, we successfully observed the disappearance of tumors implanted in four sample mice from test group of ten. High-performance RGD-conjugated dendrimer-modified GNR nanoprobes exhibit great potential in applications such as tumor targeting, imaging, and selective photothermal therapy.

Dendrimer-Modified Magnetic Nanoparticles Enhance Efficiency of Gene Delivery System

Magnetic nanoparticles (MNP) with a diameter of 8 nm were modified with different generations of polyamidoamine (PAMAM) dendrimers and mixed with antisense survivin oligodeoxynucleotide (asODN). The MNP then formed asODN-dendrimer-MNP composites, which we incubated with human tumor cell lines such as human breast cancer MCF-7, MDA-MB-435, and liver cancer HepG2 and then analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative reverse transcription-PCR, Western blotting, laser confocal microscopy, and high-resolution transmission electron microscopy. Results showed that the asODN-dendrimer-MNP composites were successfully synthesized, can enter into tumor cells within 15 min, caused marked down-regulation of the survivin gene and protein, and inhibited cell growth in dose- and time-dependent means. No.5 generation of asODN-dendrimer-MNP composites exhibits the highest efficiency for cellular transfection and inhibition. These results show that PAMAM dendrimer-modified MNPs may be a good gene delivery system and have potential applications in cancer therapy and molecular imaging diagnosis.

Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy.

Multifunctional nanoprobes are designed to own various functions such as tumor targeting, imaging and selective therapy, which offer great promise for the future of cancer prevention, diagnosis, imaging and treatment. Herein, silica was applied to replace cetyltrimethylammonium bromide (CTAB) molecules on the surface of gold nanorods (GNRs) by the classic Stöber method, thus eliminating their cytotoxicity and improving their biocompatibility. Folic acid molecule was covalently anchored on the surface of GNRs with silane coupling agent. The resultant folic acid-conjugated silica-modified GNRs show highly selective targeting, enhanced radiation therapy (RT) and photo-thermal therapy (PTT) effects on MGC803 gastric cancer cells, and also exhibited strong X-ray attenuation for in vivo X-ray and computed tomography (CT) imaging. In conclusion, the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for X-ray/CT imaging-guided targeting dual-mode enhanced RT and PTT.

Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells

We demonstrate the use of surface Zeta potential measurements as a new tool to investigate the interactions of iron oxide nanoparticles and cowpea mosaic virus (CPMV) nanoparticles with human normal breast epithelial cells (MCF10A) and cancer breast epithelial cells (MCF7) respectively. A substantial understanding in the interaction of nanoparticles with normal and cancer cells in vitro will enable the capabilities of improving diagnostic and treatment methods in cancer research, such as imaging and targeted drug delivery. A theoretical Zeta potential model is first established to show the effects of binding process and internalization process during the nanoparticle uptake by cells and the possible trends of Zeta potential change is predicted for different cell endocytosis capacities. The corresponding changes of total surface charge of cells in the form of Zeta potential measurements were then reported after incubated respectively with iron oxide nanoparticles and CPMV nanoparticles. As observed, after MCF7 and MCF10A cells were incubated respectively with two types of nanoparticles, the significant differences in their surface charge change indicate the potential role of Zeta potential as a valuable biological signature in studying the cellular interaction of nanoparticles, as well as specific cell functionality.

The Photoluminescence, Drug Delivery and Imaging Properties of Multifunctional Eu3+/Gd3+ Dual-doped Hydroxyapatite Nanorods

The design and synthesis of multifunctional systems with high biocompatibility are very significant for the future of clinical applications. Herein, we report a microwave-assisted rapid synthesis of multifunctional Eu(3+)/Gd(3+) dual-doped hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and in vivo imaging of as-prepared Eu(3+)/Gd(3+) doped HAp nanorods. The photoluminescent and magnetic multifunctions of HAp nanorods are realized by the dual-doping with Eu(3+) and Gd(3+). The PL intensity of doped HAp nanorods can be adjusted by varying Eu(3+) and Gd(3+) concentrations. The magnetization of doped HAp nanorods increases with the concentration of doped Gd(3+). The as-prepared Eu(3+)/Gd(3+)-doped HAp nanorods exhibit inappreciable toxicity to the cells in vitro. More importantly, the Eu(3+)/Gd(3+)-doped HAp nanorods show a high drug adsorption capacity and sustained drug release using ibuprofen as a model drug, and the drug release is governed by a diffusion process. Furthermore, the noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu(3+)/Gd(3+)-doped HAp nanorods with the photoluminescent function are suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that Eu(3+)/Gd(3+)-doped HAp nanorods have a potential in applications such as a multiple-model imaging agent for magnetic resonance (MR) imaging, photoluminescence imaging and computed tomography (CT) imaging. The Eu(3+)/Gd(3+) dual-doped HAp nanorods are promising for applications in the biomedical fields such as multifunctional drug delivery systems with imaging guidance.

Recent Advances in Nanotechnology Applied to Biosensors

In recent years there has been great progress the application of nanomaterials in biosensors. The importance of these to the fundamental development of biosensors has been recognized. In particular, nanomaterials such as gold nanoparticles, carbon nanotubes, magnetic nanoparticles and quantum dots have been being actively investigated for their applications in biosensors, which have become a new interdisciplinary frontier between biological detection and material science. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches, and challenges, with the aim of stimulating a broader interest in developing nanomaterial-based biosensors and improving their applications in disease diagnosis and food safety examination.

Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy.

A major challenge in nanotechnology and nanomedicine is to integrate tumor targeting, imaging, and selective therapy functions into a small single nanoparticle (<50 nm). Herein, photosensitizer-conjugated magnetic nanoparticles with ∼20 nm in diameter were strategically designed and prepared for gastric cancer imaging and therapy. The second generation photosensitizer chlorin e6 (Ce6) was covalently anchored on the surface of magnetic nanoparticles with silane coupling agent. We found that the covalently incorporated Ce6 molecules retained their spectroscopic and functional properties for near-infrared (NIR) fluorescence imaging and photodynamic therapy (PDT), and the core magnetic nanoparticles offered the functions of magnetically guided drug delivery and magnetic resonance imaging (MRI). The as-prepared single particle platform is suitable for simultaneous targeting PDT and in vivo dual-mode NIR fluorescence imaging and MRI of nude mice loaded with gastric cancer or other tumors.

MicroRNA-218 Inhibits Glioma Invasion, Migration, Proliferation, and Cancer Stem-like Cell Self-Renewal by Targeting the Polycomb Group Gene Bmi1

Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically reduces the migration, invasion, and proliferation of glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that expression of the stem cell-promoting oncogene Bmi1 was decreased after overexpression of miR-218 in glioma cells. Mechanistic investigations defined Bmi1 as a functional downstream target of miR-218 through which miR-218 ablated cell migration and proliferation. We documented that miR-218 also blocked the self-renewal of glioma stem-like cells, consistent with the suggested role of Bmi1 in stem cell growth. Finally, we showed that miR-218 regulated a broad range of genes involved in glioma cell development, including Wnt pathways that suppress glioma cell stem-like qualities. Taken together, our findings reveal miR-218 as a tumor suppressor that prevents migration, invasion, proliferation, and stem-like qualities in glioma cells.