Facilely synthesized pH-responsive fluorescent polymer dots entrapping doped and coupled doxorubicin for nucleus-targeted chemotherapy.

Doxorubicin (Dox) functionalization methods can affect the Dox loading efficiency and release capability in nanosized drug delivery systems. Herein, different Dox-functionalized (doping, coupling, and doping and coupling) fluorescent poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) polymer dots were designed and their application performance was evaluated. Polyethylene glycol-modified doxorubicin (PEG-Dox) was synthesized using a responsive hydrazone linker. PEG-DOX-doped polymer dots were self-assembled using a co-precipitation method and free PEG-Dox was further coupled on the surface of the polymer dots via an EDC-NHS coupling to prepare the PEG-Dox doped and coupled PFBT polymer dots. The hydrazone linker of PEG-Dox is responsive to the acidic environment, resulting in the doped Dox being released into the cell nucleus and the coupled Dox changes the structure of the polymer dots and accelerates the release of the doped Dox. Moreover, the coupled Dox linked via an amide bond was still on the surface of the polymer dots and retained their cytoplasmic toxicity for a synergistic effect. A high Dox carrying efficiency (weight of the loaded Dox/weight of PFBT) was achieved using the PEG-Dox doped and coupled PFBT polymer dots: 107% and 82% of Dox was released in vitro within 24 h at pH 5.5. The cytotoxicity and cell imaging were investigated in three cancer cell lines: cervical cancer cells (HeLa), lung cancer cells (NCI-H292), and glioma cells (U87-MG); the results indicate that the PEG-Dox doped and coupled PFBT polymer dots show a distinct killing efficacy and nucleus targeted capability. Moreover, in vivo tumor suppression was observed in lung tumor-bearing mice over 20 days and no weight loss and damage or inflammation of the major organs were detected using the PEG-Dox doped and coupled PFBT polymer dots.

A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer.

To enhance the diagnosis of non-small cell lung cancer (NSCLC), we prepared a dual-modal probe Cy5.5-Tf-Gd-DTPA. Gd-DTPA and near-infrared (NIR) dyes were conjugated to holo-Transferrin (Tf) sequentially, the result of ICP-AES and UV showed 25 Gd ions and 1 Cy5.5 could be loaded per protein, respectively. The calculated longitudinal relaxivity R1 of Cy5.5-Tf-DTPA-Gd was 4.21 mM-1S-1 per Gd while that of Magnevist (Gd-DTPA) was only 4.02 mM-1S-1. Confocal laser scanning microscopy and immunohistochemical analyses revealed that the Cy5.5-Tf-DTPA-Gd was localized and accumulated in cytoplasmic vesicles; the cell toxicity assay showed no apparent toxicity. MR and NIR imaging of mice with subcutaneous H1299 xenografte tumors following intravenous injection of Cy5.5-Tf-DTPA-Gd revealed a strong positive contrast of the tumors, which caused a longer lasting enhancement of the MRI signal and fluorescence signal. Taken together, these studies indicate that Cy5.5-Tf-DTPA-Gd could be a good agent for MR/NIRF dual mode applications to detect both tumor in situ and its metastasis.

Highly luminescent and photostable near-infrared fluorescent polymer dots for long-term tumor cell tracking in vivo.

Near-infrared-emitting polymer dots were prepared by encapsulating the dye NIR775 into the matrix of MEH-PPV dots using a nanoscale precipitation method, and their application for long-term tumor cell tracking in vivo is demonstrated for the first time.

Cytotoxicity, tumor targeting and PET imaging of sub-5 nm KGdF4 multifunctional rare earth nanoparticles.

Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non-small cell lung carcinoma H1299 cells was evaluated, and their application for in vitro and in vivo tumor targeted imaging has also been demonstrated.

Long-term-stable near-infrared polymer dots with ultrasmall size and narrow-band emission for imaging tumor vasculature in vivo.

Fluorescent nanoprobes have become one of the most promising classes of materials for cancer imaging. However, there remain many unresolved issues with respect to the understanding of their long-term colloidal stability and photostability in both biological systems and the environment. In this study, we report long-term-stable near-infrared (NIR) polymer dots for in vivo tumor vasculature imaging. NIR-emitting polymer dots were prepared by encapsulating an NIR dye, silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (NIR775), into a matrix of polymer dots, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), using a nanoscale precipitation method. The prepared NIR polymer dots were sub-5 nm in diameter, exhibited narrow-band NIR emission at 778 nm with a full width at half-maximum of 20 nm, and displayed a large Stokes shift (>300 nm) between the excitation and emission maxima. In addition, no significant uptake of the prepared NIR polymer dots by either human glioblastoma U87MG cells or human non-small cell lung carcinoma H1299 cells was detected. Moreover, these NIR polymer dots showed long-term colloidal stability and photostability in water at 4 °C for at least 9 months, and were able to image vasculature of xenografted U87MG tumors in living mice after intravenous injection. These results thus open new opportunities for the development of whole-body imaging of mice based on NIR polymer dots as fluorescent nanoprobes.

Robust H(infinity) output feedback control for a class of uncertain Lur'e systems with time-delays.

In this work, the analysis of robust stability and design of robust H infinity output feedback controllers for a class of Lur'e systems with both time-delays and parameter uncertainties were studied. A robust H infinity output feedback controller based on Linear Matrix Inequalities (LMIs) was developed to guarantee the robust stability and H infinity performance of the resultant closed-loop system. The presented design approach is based on the application of descriptor model transformation and Park's inequality for the bounding of cross terms and is expected to be less conservative compared to reported design methods. Finally, illustrative examples are advanced to demonstrate the superiority of the obtained method.