Leyong Zeng

BIOMEDICAL APPLICATIONS OF MAGNETIC NANOPARTICLES

In this review, the applications of magnetic nanoparticles in biomedicine are summarized and introduced in three parts. (1) A short description of magnetic nanoparticles is explained. (2) Applications of magnetic nanoparticles in biomedicine are summarized. In biology, new progress of the magnetic separation techniques based on magnetic nanoparticles is discussed. In medicine, the magnetic nanoparticles as therapeutic agents (particularly as a hyperthermia agent, a targeted drug delivery carrier, and a magnetofection agent) as well as contrast agents in magnetic resonance imaging (MRI) are explained in detail. (3) A discussion and remarking conclusion of magnetic nanoparticles in biomedical applications are described. Finally, a perspective of the magnetic nanoparticles in biomedicine in future is also described.

A one-step colorimetric method of analysis detection of Hg2+ based on an in situ formation of Au@HgS core–shell structures

A new approach for the detection of Hg(2+) is reported based on color changes from which gold nanoparticles (Au NPs) are surrounded by a layer of HgS quantum dots to form in situ Au@HgS core-shell nanostructures. The surface plasmon resonance (SPR) absorption of the gold core was changed due to a shell layer of HgS formed on the surface of the Au NPs, which brings the colour change of the aqueous solution. Therefore, Hg(2+) can be recognized by visualizing the colour change of the Au@HgS core-shell nanostructures, and can be detected quantitatively by measurement of the UV-vis spectra. Some effects on the detection of Hg(2+) were investigated in detail. This method was used to detect Hg(2+) with excellent selectivity and high sensitivity. In our method, the lowest detected concentrations for mercury ions were 5.0 × 10(-6) M observed by the naked eye and 0.486 nM as measured by UV-vis spectra. At the range from 8.0 × 10(-5) to 1.0 × 10(-8) M of Hg(2+), this method was shown to have a good linear relationship.

A Near Infrared Light Triggered Hydrogenated Black TiO2 for Cancer Photothermal Therapy

White TiO2 nanoparticles (NPs) have been widely used for cancer photodynamic therapy based on their ultraviolet light-triggered properties. To date, biomedical applications using white TiO2 NPs have been limited, since ultraviolet light is a well-known mutagen and shallow penetration. This work is the first report about hydrogenated black TiO2 (H-TiO2 ) NPs with near infrared absorption explored as photothermal agent for cancer photothermal therapy to circumvent the obstacle of ultraviolet light excitation. Here, it is shown that photothermal effect of H-TiO2 NPs can be attributed to their dramatically enhanced nonradiative recombination. After polyethylene glycol (PEG) coating, H-TiO2 -PEG NPs exhibit high photothermal conversion efficiency of 40.8%, and stable size distribution in serum solution. The toxicity and cancer therapy effect of H-TiO2 -PEG NPs are relative systemically evaluated in vitro and in vivo. The findings herein demonstrate that infrared-irradiated H-TiO2 -PEG NPs exhibit low toxicity, high efficiency as a photothermal agent for cancer therapy, and are promising for further biomedical applications.

A colorimetric assay method for Co2+ based on thioglycolic acid functionalized hexadecyl trimethyl ammonium bromide modified Au nanoparticles (NPs)

A simple, rapid and sensitive colorimetric assay method for detection of Co(2+) through thioglycollic acid (TGA) functionalized hexadecyl trimethyl ammonium bromide (CTAB) modified Au NPs has been discovered in our work. TGA functionalized CTAB modified Au NPs can be aggregated quickly in the presence of Co(2+) through a cooperative metal-ligand interaction. Transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDS), and UV-vis spectra were used to characterize the Au NPs aggregation. The presence of Co(2+) is monitored by a colorimetric response of functionalized Au NPs, and had a detection limit of 3.0 × 10(-7) M. Moreover, the selectivity of this method has been investigated by comparing with other metal ions (Hg(2+), Na(+), Cu(2+), Cd(2+), Ba(2+), Pb(2+), Mn(2+), Ni(2+), Zn(2+), Fe(2+) and Fe(3+)).

Multifunctional photosensitizer-conjugated core–shell Fe3O4@NaYF4:Yb/Er nanocomplexes and their applications in T2-weighted magnetic resonance/upconversion luminescence imaging and photodynamic therapy of cancer cells

Due to non-invasive deep imaging and therapy, multifunctional agents of magnetic resonance (MR)/upconversion luminescence (UCL) imaging and photodynamic therapy (PDT) play an important role in clinical diagnosis and treatment of cancers, and also in the assessment of therapy effect. In this paper, tetra-sulfonic phthalocyanine aluminium (AlPcS4) photosensitizers-conjugated Fe3O4@NaYF4:Yb/Er (NPs-AlPcS4) nanocomplexes were synthesized for the T2-weighted MR/UCL imaging and PDT of cancer cells. The PEG-coated Fe3O4@NaYF4:Yb/Er nanoparticles (NPs) with a core–shell structure showed strong T2-weighted MR relaxivity (r2 = 42.131 mM−1 s−1) and UCL emission in the visible region (the bands at about 654–674 nm, 545 nm and 524 nm), and were conjugated successfully with AlPcS4 photosensitizer by electrostatic interaction. By direct observation of XFM and staining with Prussian blue, the element distribution and location of NPs in MCF-7 cells were characterized, respectively. Under irradiation from a 980 nm laser, the death ratio of MCF-7 cells incubated with NPs-AlPcS4 nanocomplexes could be up to about 70%. The results indicated that the as-prepared NPs-AlPcS4 nanocomplexes would be a potential candidate as multifunctional nanoprobes for the dual-modal T2-weighted MR/UCL imaging and PDT of cancers in the future.

Raman Reporter-coupled Agcore@Aushell Nanostars for in Vivo Improved Surface Enhanced Raman Scattering Imaging and Near-infrared-Triggered Photothermal Therapy in Breast Cancers

Noble-metal nanomaterials were widely investigated as theranostic systems for surface enhanced Raman scattering (SERS) imaging, and also for photothermal therapy (PTT) of cancers. However, it was still a major challenge to explore multifunctional nanoprobes with high performance, high stability, and low toxicity. In this work, Raman reporter (DTTC)-coupled Agcore@Aushell nanostars (Ag@Au-DTTC) were synthesized and investigated for in vivo improved SERS imaging and near-infrared (NIR)-triggered PTT of breast cancers. By the two-step coupling of DTTC, the SERS signal was improved obviously, and the cytotoxicity of nanoparticles was also decreased by coating Au nanostars onto Ag nanoparticles. The as-prepared Ag@Au-DTTC nanostars showed high photostability and excellent photothermal performance, in which the photothermal conversion efficiency was up to 79.01% under the irradiation of an 808 nm laser. The in vitro and in vivo SERS measurements of Ag@Au-DTTC nanostars showed that the many sharp and narrow Raman peaks located at 508, 782, 844, 1135, 1242, 1331, 1464, 1510, and 1580 cm(-1) could be obviously observed in MCF-7 cells and in MCF-7 tumor-bearing nude mice, compared with that in pure DTTC. In 14-day treatments, the tumor volume of MCF-7 tumor-bearing nude mice injected with Ag@Au-DTTC nanostars and irradiated by an 808 nm laser almost disappeared. This study demonstrated that the as-prepared Ag@Au-DTTC nanostars could be excellent multifunctional agents for improved SERS imaging and NIR-triggered PTT of breast cancers with low risk.

Enhanced doxorubicin transport to multidrug resistant breast cancer cells via TiO2 nanocarriers

In order to overcome the multidrug resistance of breast cancer cells, doxorubicin was loaded onto TiO2 nanoparticles in which the electrostatic interactions hold the drug and the nanoparticles together. The anticancer activity of this nanocomposite was evaluated in multidrug resistant breast cancer cells. In nanocomposite treated MCF-7/ADM cells, drug accumulation increased with enhanced anticancer activity about 2.4 times compared to that of doxorubicin alone. The potential mechanism of enhanced drug accumulation is ascribed to the fact that the nanocomposite directly transports the drugs into cells via internalization, bypassing the P-glycoprotein mediated doxorubicin pumping system. Our results reinforce that the nanocomposite, as a pH controlled drug release system, could be used to overcome multidrug resistance of human breast cancer cells.

The enhanced chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers in an orthotopic breast tumor bearing mouse model

Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and have high levels of systemic toxicity. One of the most prominent progresses in improving drug delivery efficiency is through exploring various types of nanoparticles (NPs) as drug carriers. Recent studies have demonstrated that titanium dioxide (TiO2) nanocarriers have potential for drug delivery and therapy even in multidrug resistant cancers in vitro. Moreover, it was proved that the anticancer activity of doxorubicin (DOX) was enhanced by loading onto TiO2 nanoparticles in breast cancer cells in vitro. However, there is no evidence from the animal model in vivo, which is a critical step for their further clinical applications. The aim of this study was to explore novel TiO2-PEG-DOX nanoparticles, the DOX loaded polyethylene glycol (PEG) coated TiO2 nanocarriers, and investigate their potential application in enabling controlled drug release and enhancing the chemotherapeutic efficacy of DOX in the orthotopic breast tumor bearing mice. The tumor growth and drug treatment efficacy were dynamically monitored by bioluminescence imaging (BLI), and the safety of NPs for in vivo usage was also evaluated. It was found that TiO2-PEG-DOX nanoparticles possessed improved antitumor efficacy without observable side effects compared to the free DOX treatment. Our study suggested that the PEG coated TiO2 nanocarrier is a safe and potential platform for the efficient drug delivery and minimizing the systemic toxicity of chemotherapeutic agents. It has been proved for the first time that TiO2-based nanocarriers enhance the chemotherapeutic effects of doxorubicin in vivo.

Gold nanostars functionalized with amine-terminated PEG for X-ray/CT imaging and photothermal therapy

Multifunctional gold nanostructures effective at photothermal therapy (PTT) and high-quality X-ray/computed tomography (CT) imaging have drawn much attention in recent research. In particular, the development of improved PTT against cancer has been a particularly focused area of research for which the clinical need is great. Since the intracellular concentration of gold nanostructures is critical for their therapeutic photothermal efficacy, we decorated gold nanostructures with positively charged polyethylene glycol (PEG) to boost their degree of uptake by the cell. Herein gold nanostars (GNSs) were decorated with amine-terminated PEG (GNS-PEG-NH2) and methoxy-terminated PEG (GNS-mPEG). PEGylated GNSs showed good dispersivity, high stability and low cytotoxicity. Moreover, compared with GNS-mPEG, GNS-PEG-NH2 exhibited superior thermal therapeutic efficacy against breast tumor cells due to their higher cellular uptake. Measurement of the X-ray absorption coefficient revealed that the attenuation of GNS-PEG-NH2 was about 3.6-fold higher than that of the commercial CT contrast agent iodixanol at the concentration of 25 mg L-1. Importantly, GNS-PEG-NH2 also exhibited effective tumor therapeutic efficacy in vivo, and the tumor sites injected with GNS-PEG-NH2 showed high contrast X-ray/CT imaging. And most of the injected GNS-PEG-NH2 was cleared from tumors 15 days post-injection, indicating rapid clearance and minimal toxicity of GNS-PEG-NH2. Such PEGylated GNSs, when used for producing high-contrast images to guide enhanced PTT therapy, may thus provide new opportunities for the development of cancer theranostics.

Near-infrared Light Responsive Upconversion Nanoparticles for Imaging, Drug Delivery and Therapy of Cancers

Cancers have become serious threat to human health and life, and they are critical to develop safe and effective theranostic methods for diagnosis and therapy of tumors. In recent years, real time cancer theranostic visualization systems (RT-CTVS) based on light-responsive nanoparticles have been developed. Especially, upconversion nanoparticles (UCNPs) have excellent optical properties and unique near-infrared (NIR) responsive. The minimized photodamage, low autofluorescence and high penetration depth can be achieved with UCNPs. Therefore, UCNPs are widely used in real time NIR mediated visualization systems of cancer diagnosis and therapy. In this review, we focus on the latest developments of rare earth ions doped upconversion fluorescence nanoparticles. First, the synthesis methods of UCNPs were briefly introduced. Second, the strategies of UCNPs surface modifications, including the ligand exchange, ligand oxidation, ligand interaction, ligand free synthesis, layer by layer growth and surface silanization were summarized. Third, the recent research progress in applying UCNPs to construct NIR light stimuli-responsive RT-CTVS, including imaging, drug delivery and photodynamic therapy (PDT) were highlighted. Finally, some of the current problems and future effort directions in these fields were also proposed.