Smart micelle@polydopamine core-shell nanoparticles for highly effective chemo-photothermal combination therapy.

In this investigation, we have designed and synthesized a novel core-shell polymer nanoparticle system for highly effective chemo-photothermal combination therapy. A nanoscale DSPE-PEG micelle encapsulating doxorubicin (Dox-M) was designed as a core, and then modified by a polydopamine (PDA) shell for photothermal therapy and bortezomib (Btz) administration (Dox-M@PDA-Btz). The facile conjugation of Btz to the catechol-containing PDA shell can form a reversible pH-sensitive boronic acid-catechol conjugate to create a stimuli-responsive drug carrier system. As expected, the micelle@PDA core-shell nanoparticles exhibited satisfactory photothermal efficiency, which has potential for thermal ablation of malignant tissues. In addition, on account of the PDA modification, both Dox and Btz release processes were pH-dependent and NIR-dependent. Both in vitro and in vivo studies illustrated that the Dox-M@PDA-Btz nanoparticles coupled with laser irradiation could enhance the cytotoxicity, and thus combinational therapy efficacy was achieved when integrating Dox, Btz, and PDA into a single nanoplatform. Altogether, our current study indicated that the micelle@polydopamine core-shell nanoparticles could be applied for NIR/pH-responsive sustained-release and synergized chemo-photothermal therapy for breast cancer.

Hyaluronic acid functional amphipathic and redox-responsive polymer particles for the co-delivery of doxorubicin and cyclopamine to eradicate breast cancer cells and cancer stem cells.

Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.

pH-responsive biocompatible fluorescent polymer nanoparticles based on phenylboronic acid for intracellular imaging and drug delivery.

To address current medical challenges, there is an urgent need to develop drug delivery systems with multiple functions, such as simultaneous stimuli-responsive drug release and real-time imaging. Biocompatible polymers have great potential for constructing smart multifunctional drug-delivery systems through grafting with other functional ligands. More importantly, novel biocompatible polymers with intrinsic fluorescence emission can work as theranostic nanomedicines for real-time imaging and drug delivery. Herein, we developed a highly fluorescent nanoparticle based on a phenylboronic acid-modified poly(lactic acid)-poly(ethyleneimine)(PLA-PEI) copolymer loaded with doxorubicin (Dox) for intracellular imaging and pH-responsive drug delivery. The nanoparticles exhibited superior fluorescence properties, such as fluorescence stability, no blinking and excitation-dependent fluorescence behavior. The Dox-loaded fluorescent nanoparticles showed pH-responsive drug release and were more effective in suppressing the proliferation of MCF-7 cells. In addition, the biocompatible fluorescent nanoparticles could be used as a tool for intracellular imaging and drug delivery, and the process of endosomal escape was traced by real-time imaging. These pH-responsive and biocompatible fluorescent polymer nanoparticles, based on phenylboronic acid, are promising tools for intracellular imaging and drug delivery.

Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer.

Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene Bcl-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-1 signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

Ultrabright and multicolorful fluorescence of amphiphilic polyethyleneimine polymer dots for efficiently combined imaging and therapy.

Multifunctional nanoparticles as theranostic tools hold great potential for its unique and efficient way to visualize the process of disease treatment. However, the toxicity of conventional fluorescent labels and difficulty of functionalization limit their widespread use. Recently, a number of amino-rich polymers have demonstrated high luminescent fluorescence but rarely showed potential for in vivo imaging due to their blue fluorescence. Here, a general route has been found to construct polymer-based multifunctional nanoparticles for combined imaging and drug delivering. The weak fluorescent polyethyleneimine (PEI) has been conjugated with hydrophobic polylactide as the amphiphilic PEI for construction of nanoparticles which showed bright and multicolor fluorescence with high drug loading capacity. The paclitaxel-loaded nanoparticles showed significant therapy effect in contrast to the free paclitaxel. Meanwhile, fluorescence imaging of the nanoparticles showed accumulation around tumor. These results demonstrate a new type of polymer-based multifunctional nanoparticles for imaging-guided drug delivery.

Investigation on partially coherent vector beams and their propagation and focusing properties.

The propagation and focusing properties of partially coherent vector beams including radially polarized and azimuthally polarized (AP) beams are theoretically and experimentally investigated. The beam profile of a partially coherent radially or AP beam can be shaped by adjusting the initial spatial coherence length. The dark hollow, flat-topped, and Gaussian beam spots can be obtained, which will be useful in trapping particles. The experimental observations are consistent with the theoretical results.

Tight focusing properties of hybridly polarized vector beams.

We theoretically investigate the tight focusing properties of hybridly polarized vector beams. Some numerical results are obtained to illustrate the intensity, phase, and polarization of tightly focused hybridly polarized vector beams. It is shown that the shape of the focal pattern may change from an elliptical beam to a ring focus with increasing radial index. The phase distribution around the tightly focused ring is shown to be the helical phase profile, indicating that the radial-variant spin angular momentum of hybridly polarized vector beams can be converted into the radial-variant orbital angular momentum.

Generation of super-length optical needle by focusing hybridly polarized vector beams through a dielectric interface.

A super-length optical needle (~14λ) of strong transversally polarized field with homogeneous intensity along the optical axis and subdiffraction beam size (~0.9λ) can be generated by focusing a hybridly polarized vector beam through a dielectric interface with an annular high-NA lens. Moreover, it is found that the polarization of the cross section near the focal plane is radial variant. Such a nondiffracting optical needle may have applications in atom-optical experiments, such as with atom trap and atom switches.