Specific Targeting Capability Research Articles

Dual tumor-targeted multifunctional magnetic hyaluronic acid micelles for enhanced MR imaging and combined photothermal-chemotherapy

Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C16 copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period. Moreover, the specific targeting capability based on CD44 recptor-mediated endocytosis and the enhanced targeting efficacy by in presence of external magnetic field were investigated. The clustered SPIONs within micelles exerted excellent contrast effect with high r2 relaxivity in MR phantom test. Furthermore, the multifunctional micelles could readily convert light to heat to hyperthermia temperature upon near infrared light irradition and induce photothermal ablation to breast cancer cells. The combined photothermal therapy with DTX-mediated chemotherapy of the developed multifunctional polymeric micells could generate a synergistic therapeutic effect. Based on these findings, the resulting multifunctional micelles may provide high potential for multimodality theragnosis of cancer.

Characterization of ginger essential oil/palygorskite composite (GEO-PGS) and its anti-bacteria activity

To explore a novel kind of anti-bacterial composite material having the excellent antibacterial ability, stability and specific-targeting capability, palygorskite (PGS) was used as the carrier of ginger essential oil (GEO) and a novel kind of composite GEO-PGS was prepared by ion exchange process. The characterization and the antibacterial activity of GEO-PGS was investigated in this study. Results of FTIR, XPS, XRD,TG analysis and SEM observation demonstrated the combination of GEO and PGS, GEO was absorbed on the surface of PGS, and the content of GEO in the composite was estimated to be 18.66%. Results of minimal inhibitory concentration (MIC) analysis, growth curve and Gram staining analysis of Staphylococci aureus and Escherichia coli exposed to GEO-PGS showed that GEO-PGS had much higher antibacterial activity than GEO, and GEO-PGS had the specific-targeting antibacterial capability. Moreover, GEO-PGS showed the characteristics of thermo-stability, acidity and alkalinity-resistance in exerting its anti-bacteria activity. In conclusion, the novel composite GEO-PGS combined the bacteria-absorbent activity of PGS and the antibacterial activity of GEO, suggesting the great potential application of GEO-PGS as the novel composite substance with high antibacterial activity.

Stable Upconversion Nanohybrid Particles for Specific Prostate Cancer Cell Immunodetection.

Prostate cancer is one of the male killing diseases and early detection of prostate cancer is the key for better treatment and lower cost. However, the number of prostate cancer cells is low at the early stage, so it is very challenging to detect. In this study, we successfully designed and developed upconversion immune-nanohybrids (UINBs) with sustainable stability in a physiological environment, stable optical properties and highly specific targeting capability for early-stage prostate cancer cell detection. The developed UINBs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and luminescence spectroscopy. The targeting function of the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay and western blot analysis. The UINB system is able to specifically detect prostate cancer cells with stable and background-free luminescent signals for highly sensitive prostate cancer cell detection. This work demonstrates a versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive diseased cell detection.

Controlled release and long-term antibacterial activity of reduced graphene oxide/quaternary ammonium salt nanocomposites prepared by non-covalent modification

In order to control the long-term antibacterial property of quaternary ammonium salts, dodecyl dimethyl benzyl ammonium chloride (rGO-1227) and rGO-bromohexadecyl pyridine (rGO-CPB) were self-assembled on surfaces of reduced graphene oxide (rGO) via π-π interactions. The obtained rGO-1227 and rGO-CPB nanocompounds were characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM).The antibacterial activities were evaluated on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Both rGO-CPB and rGO-1227 reduced the cytotoxicity of the pure antimicrobial agents and presented strong antimicrobial properties. Especially, CPB could be loaded efficiently on the surface of rGO via π-π conjugate effect, which resulted in a nanocomposite presenting a long-term antibacterial capability due to the more important quantity of free π electrons compared to that of 1227. When comparing the advantages of both prepared nanocomposites, rGO-CPB displayed a better specific-targeting capability and a longer-term antibacterial property.

Multicomponent polymeric nanoparticles enhancing intracellular drug release in cancer cells.

Three kinds of amphiphilic copolymer, that is, poly(ε-caprolactone)-SS-poly(ethylene glycol) (PCL-SS-PEG), poly(ε-caprolactone)-polyethylenimine (PCL-PEI), and poly(ε-caprolactone)-polyethylenimine-folate (PCL-PEI-Fol) were synthesized and self-assembled into surface engineered hybrid nanoparticles (NPs). Morphological studies elucidated the stable, spherical, and uniform sandwich structure of the NPs. PCL-PEI and PCL-SS-PEG segments have introduced pH and reduction responsive characteristics in these NPs, while PCL-PEI-FA copolymers could provide specific targeting capability to cancer cells. The stimuli responsive capabilities of these NPs were carried out. Negative-to-positive charge reversible property, in response to the pH change, was investigated by zeta potential and nuclear magnetic resonance (NMR) measurements. The structure cleavage, due to redox gradient, was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). These NPs showed controlled degradation, better drug release, less toxicity, and effective uptake in MCF-7 breast cancer cells. These multifunctional NPs showed promising potential in the treatment of cancer.

PET imaging of neovascularization with (68)Ga-3PRGD2 for assessing tumor early response to Endostar antiangiogenic therapy.

Antiangiogenic therapy is an effective strategy to inhibit tumor growth. Endostar, as an approved antiangiogenesis agent, inhibits the newborn vascular endothelial cells, causing the decrease of integrin αvβ3 expression. Radiolabeled 3PRGD2, a novel PEGlayted RGD dimer probe (PEG4-E[PEG4-c(RGDfK)]2) showed highly specific targeting capability to integrin αvβ3, which could be used for monitoring the efficacy of Endostar antiangiogenic therapy. In this study, (68)Ga-3PRGD2 PET imaging was performed in Endostar treated/untreated Lewis Lung Carcinoma (LLC) mice on days 3, 7, 14, and 21 post-treatment for monitoring the tumor response to Endostar treatment, with the (18)F-FDG imaging as control. As a result, (68)Ga-3PRGD2 PET reflected the tumor response to Endostar antiangiogenic therapy much earlier (day 3 post-treatment vs day 14 post-treatment) and more accurately than that of (18)F-FDG metabolic imaging, which provides new opportunities to develop individualized therapeutic approaches, establish optimized dosages and dose intervals for effective treatment that improve the survival rate of patients.

Spatiotemporally programmable surface engineered nanoparticles for effective anticancer drug delivery.

Surface engineered nanoparticles (NPs) are fabricated from polycaprolactone-polyethylenimine-folic acid (PCL-PEI-FA) and polycaprolactone-S-S-polyethylene glycol (PCL-S-S-PEG) copolymers. FESEM reveals the core-shell structure of these NPs of about 230 nm size. It is assumed that the inner cores of these NPs are composed of PCL, while the outer shells are adorned with PEG and folic acid, introducing a stealthy nature and specific targeting capability. Moreover, the disulfide bonds in the PCL-S-S-PEG copolymers provide a reduction-induced degradation characteristic in these NPs. Cell line experiments demonstrate the enhanced endocytosis and cytotoxicity of these NPs. Thus PCL-PEI-FA/PCL-S-S-PEG NPs could be a better candidate for the tumor specific delivery of hydrophobic drugs.

Development of bovine serum albumin-modified hybrid nanoclusters for magnetofluorescence imaging and drug delivery

Magnetofluorescent nanoclusters containing oil-soluble nanoparticles of MnFe2O4and AgInS2–ZnS QDs are prepared. The nanoclusters possess photoluminescent and magnetic properties as well as an excellent specific targeting and drug delivery capability on HeLa cancer cell.

Light-up bioprobe with aggregation-induced emission characteristics for real-time apoptosis imaging in target cancer cells.

Specific bioprobes that are capable of real-time and targeted monitoring and imaging of cancer cell apoptosis are highly desirable for cancer diagnosis and the evaluation of cancer therapy efficacy. In this work, an asymmetric fluorescent light-up bioprobe with aggregation-induced emission (AIE) characteristics was designed and synthesized by the conjugation of two different hydrophilic peptides, caspase-specific Asp-Glu-Val-Asp (DEVD) and cyclic Arg-Gly-Asp (cRGD), onto a typical AIE luminogen of a tetraphenylsilole (TPS) unit. The asymmetric probe is almost non-emissive in aqueous solution and its fluorescence is significantly switched on in the presence of caspase-3. The fluorescence turn-on is due to the cleavage of the DEVD moiety by caspase-3, and the aggregation of released TPS-cRGD residues, which restricts the intramolecular rotations of TPS phenyl rings and populates the radiative decay channels. Application of the asymmetric light-up probe for real-time targeted imaging of cancer cell apoptosis is successfully demonstrated using integrin αvβ3 receptor overexpressing U87MG human glioblastoma cells as an example. The probe shows specific targeting capability to U87MG cancer cells by virtue of the efficient binding between cRGD and integrin αvβ3 receptors and is able to real-time monitor and image cancer cell apoptosis in a specific and sensitive manner.

On/Off National Type

Although every classification in the Latin script type is concerned with either a period, forms, or shapes of letterforms, and no category deals with the national feel of type, the absence of such a category does not exclude the existence of faces with emotional impact on viewers as well as their specific targeting capability. What is a national font? Are there any national fonts? Are there any fonts resembling a culture, a country, or a nation? The importance of having fonts resembling national feel, look and characteristics tends to be more adequate and urgent these days than it was in history. Behind the shapes and forms (Fig. 1) of a vast variety of different fonts, there must be some of them which not only prove to carry national features, but show the ability to be recognised by viewers as a label of a country, the origin of products and companies, or as communities with similar beliefs or interests. The power of faces' visage might be underestimated in the world of globalisation we are living in, and when strong marketing campaigns can rely on type with its ability to show characteristics of products, companies, or even governments.

Synergistic Antibacterial Brilliant Blue/Reduced Graphene Oxide/Quaternary Phosphonium Salt Composite with Excellent Water Solubility and Specific Targeting Capability

A water-soluble brilliant blue/reduced graphene oxide/tetradecyltriphenylphosphonium bromide composite (BB-rGO-TTP) was prepared by using noncovalent brilliant blue-functionalized reduced graphene oxide (BB-rGO) as the tetradecyltriphenylphosphonium bromide (TTP) carrier. Antibacterial performance of this novel composite was investigated for both Gram-positive and Gram-negative bacteria. The results showed that the novel BB-rGO-TTP, combing the advantages of graphene and TTP, displayed excellent synergistic antibacterial activity, specific targeting capability, water solubility, and mild cytotoxicity, suggesting the great potential application as sprayable graphene-based antibacterial solutions.

Research Spotlight - Radioimmunotherapy: Optimizing Delivery to Solid Tumors

Radioimmunotherapy (RIT) is a cancer treatment that exploits the specific targeting capability of monoclonal antibodies to deliver cytotoxic radionuclides to antigen-expressing tumor cells or stromal targets. While this has been extremely successful in the treatment of hematologic malignancies, RIT of solid tumors has produced less prolonged effects. In our laboratory, we have developed a bench-to-bedside translational pipeline with the aim of optimizing RIT for solid tumors. We will show how preclinical models of colorectal adenocarcinoma were initially used to study reciprocal interactions between elements of the tumor microenvironment and RIT and to test novel therapeutic strategies. These studies were then used to facilitate the design of novel trials carried out in close collaboration with our clinical colleagues.

Monoclonal antibody-functionalized mesoporous silica nanoparticles (MSN) for selective targeting breast cancer cells

In this work, we conjugate anti-HER2/neu mAb (monoclonal antibody) to green fluorescent dye loaded mesoporous silica nanoparticles (Her-Dye@MSN) through a polyethylene glycol (MW = 5000) spacer. We examine their targeting properties toward HER2/neu over-expressing breast cancer cells and their internalization into the cells. Her-Dye@MSN nanoparticles exhibit a high targeting efficiency and the specific targeting capability is strongly affected by the mAb density on the Her-Dye@MSN. The time-course of competitive experiments with free antibody indicates that Her-Dye@MSN serves as a multivalent ligand. Moreover, Her-Dye@MSNs are internalized into cells through a receptor-mediated endocytosis and may escape from endosome to cytosol. The results reported here further support the potential of MSNs as a multifunctional smart nanocarriers for cell imaging and drug delivery.