RGD-conjugated silica-coated gold nanorods on the surface of carbon nanotubes for targeted photoacoustic imaging of gastric cancer

Herein, we reported for the first time that RGD-conjugated silica-coated gold nanorods on the surface of multiwalled carbon nanotubes were successfully used for targeted photoacoustic imaging of in vivo gastric cancer cells. A simple strategy was used to attach covalently silica-coated gold nanorods (sGNRs) onto the surface of multiwalled carbon nanotubes (MWNTs) to fabricate a hybrid nanostructure. The cross-linked reaction occurred through the combination of carboxyl groups on the MWNTs and the amino group on the surface of sGNRs modified with a silane coupling agent. RGD peptides were conjugated with the sGNR/MWNT nanostructure; resultant RGD-conjugated sGNR/MWNT probes were investigated for their influences on viability of MGC803 and GES-1 cells. The nude mice models loaded with gastric cancer cells were prepared, the RGD-conjugated sGNR/MWNT probes were injected into gastric cancer-bearing nude mice models via the tail vein, and the nude mice were observed by an optoacoustic imaging system. Results showed that RGD-conjugated sGNR/MWNT probes showed good water solubility and low cellular toxicity, could target in vivo gastric cancer cells, and obtained strong photoacoustic imaging in the nude model. RGD-conjugated sGNR/MWNT probes will own great potential in applications such as targeted photoacoustic imaging and photothermal therapy in the near future.     

BRCAA1 antibody- and Her2 antibody-conjugated amphiphilic polymer engineered CdSe/ZnS quantum dots for targeted imaging of gastric cancer

Successful development of safe and highly effective nanoprobes for targeted imaging of in vivo early gastric cancer is a great challenge. Herein, we choose the CdSe/ZnS (core-shell) quantum dots (QDs) as prototypical materials, synthesized one kind of a new amphiphilic polymer including dentate-like alkyl chains and multiple carboxyl groups, and then used the prepared amphiphilic polymer to modify QDs. The resultant amphiphilic polymer engineered QDs (PQDs) were conjugated with BRCAA1 and Her2 monoclonal antibody, and prepared BRCAA1 antibody- and Her2 antibody-conjugated QDs were used for in vitro MGC803 cell labeling and in vivo targeted imaging of gastric cancer cells. Results showed that the PQDs exhibited good water solubility, strong photoluminescence (PL) intensity, and good biocompatibility. BRCAA1 antibody- and Her2 antibody-conjugated QD nanoprobes successfully realized targeted imaging of in vivo gastric cancer MGC803 cells. In conclusion, BRCAA1 antibody- and Her2 antibody-conjugated PQDs have great potential in applications such as single cell labeling and in vivo tracking, and targeted imaging and therapeutic effects'' evaluation of in vivo early gastric cancer cells in the near future.     

Fluorescent magnetic nanoparticle-labeled mesenchymal stem cells for targeted imaging and hyperthermia therapy of in vivo gastric cancer

How to find early gastric cancer cells in vivo is a great challenge for the diagnosis and therapy of gastric cancer. This study is aimed at investigating the feasibility of using fluorescent magnetic nanoparticle (FMNP)-labeled mesenchymal stem cells (MSCs) to realize targeted imaging and hyperthermia therapy of in vivo gastric cancer. The primary cultured mouse marrow MSCs were labeled with amino-modified FMNPs then intravenously injected into mouse model with subcutaneous gastric tumor, and then, the in vivo distribution of FMNP-labeled MSCs was observed by using fluorescence imaging system and magnetic resonance imaging system. After FMNP-labeled MSCs arrived in local tumor tissues, subcutaneous tumor tissues in nude mice were treated under external alternating magnetic field. The possible mechanism of MSCs targeting gastric cancer was investigated by using a micro-multiwell chemotaxis chamber assay. Results show that MSCs were labeled with FMNPs efficiently and kept stable fluorescent signal and magnetic properties within 14 days, FMNP-labeled MSCs could target and image in vivo gastric cancer cells after being intravenously injected for 14 days, FMNP-labeled MSCs could significantly inhibit the growth of in vivo gastric cancer because of hyperthermia effects, and CCL19/CCR7 and CXCL12/CXCR4 axis loops may play key roles in the targeting of MSCs to in vivo gastric cancer. In conclusion, FMNP-labeled MSCs could target in vivo gastric cancer cells and have great potential in applications such as imaging, diagnosis, and hyperthermia therapy of early gastric cancer in the near future.     

Size-regulated group separation of CoFe2O4 nanoparticles using centrifuge and their magnetic resonance contrast properties

Magnetic nanoparticle (MNP)-based magnetic resonance imaging (MRI) contrast agents (CAs) have been the subject of extensive research over recent decades. The particle size of MNPs varies widely and is known to influence their physicochemical and pharmacokinetic properties. There are two commonly used methods for synthesizing MNPs, organometallic and aqueous solution coprecipitation. The former has the advantage of being able to control the particle size more effectively; however, the resulting particles require a hydrophilic coating in order to be rendered water soluble. The MNPs produced using the latter method are intrinsically water soluble, but they have a relatively wide particle size distribution. Size-controlled water-soluble MNPs have great potential as MRI CAs and in cell sorting and labeling applications. In the present study, we synthesized CoFe₂O₄ MNPs using an aqueous solution coprecipitation method. The MNPs were subsequently separated into four groups depending on size, by the use of centrifugation at different speeds. The crystal shapes and size distributions of the particles in the four groups were measured and confirmed by transmission electron microscopy and dynamic light scattering. Using X-ray diffraction analysis, the MNPs were found to have an inverse spinel structure. Four MNP groups with well-selected semi-Gaussian-like diameter distributions were obtained, with measured T₂ relaxivities (r₂) at 4.7 T and room temperature in the range of 60 to 300 mM⁻¹s⁻¹, depending on the particle size. This size regulation method has great promise for applications that require homogeneous-sized MNPs made by an aqueous solution coprecipitation method. Any group of the CoFe₂O₄ MNPs could be used as initial base cores of MRI T₂ CAs, with almost unique T₂ relaxivity owing to size regulation. The methodology reported here opens up many possibilities for biosensing applications and disease diagnosis.

PACS

75.75.Fk, 78.67.Bf, 61.46.Df     

Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe₂O₄ nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.     

Graphene oxide/zinc ferrite nanocomposite loaded with doxorubicin as a potential theranostic mediu in cancer therapy and magnetic resonance imaging

Hybrid functional biomaterials are attracting increasing interest due to their biocompatibility and therapeutic and diagnostic characteristics. The theranostic properties of functional biomaterials favor their application. When these materials are responded to stimuli, they confer target site delivery. Although various types of nanocomposites have been developed for drug delivery and diagnostics, no ideal composites have been reported yet. Here, we report the synthesis of graphene oxide–zinc ferrite hybrid nanocomposites (GO-ZnFe₂O₄) conjugated with doxorubicin (GO-ZnFe₂O₄/DOX) for cancer therapy and magnetic resonance (MR) imaging-based diagnosis. The optical properties, crystal phase, particle size, functional groups, elemental composition, surface morphology, and magnetism of GO-ZnFe₂O₄ nanocomposites were characterized using state-of-the-art available techniques, including Fourier-Transform Infrared Spectroscopy (FTIR), Ultraviolet visible spectroscopy (UV–Vis), Transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Dynamic light scattering (DLS), Vibrating sample magneto meter (VSM) Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectra (XPS). The in vitro analysis showed that GO-ZnFe₂O₄ conjugated with DOX is more cytotoxic than GO-ZnFe₂O₄. GO-ZnFe₂O₄/DOX induced the production of reactive oxygen species (ROS), which induced damage to nuclear DNA and mitochondrial DNA (mtDNA) when internalized by cells. This damage consequently drove mitochondrial malfunction and ultimately the apoptosis of cancer cells. Further studies were performed to investigate the diagnostic efficacy of these nanocomposites using MR imaging. GO-ZnFe₂O₄/DOX nanocomposites were developed and successfully employed in the MR imaging of HeLa cells. As shown in the present study, GO-ZnFe₂O₄/DOX might play a potential role in the development of chemotherapy and noninvasive MR imaging of tumor cells.     

Synthesis and evaluation of paramagnetic particulates as contrast agents for magnetic resonance imaging (MRI)

Formulations based on novel particulate ion-exchange resins, containing a wide range of paramagnetic transition and rare-earth metals bound to their surfaces, have been synthesised as potential contrast agents for the magnetic resonance imaging (MRI) of the gastro-intestinal (GI) tract of man. They have been evaluated in terms of their effects upon the spin-lattice (R₁) and spin-spin (R₂) relaxation rates of the protons of water. Careful selection of the polymer, spacer-arm, ligand and paramagnetic ion provides a means for subtle molecular tailoring. Further potential applications have been highlighted based on the observed properties of such formulations.