Xiuli Yue

Uniform polypyrrole nanoparticles with high photothermal conversion efficiency for photothermal ablation of cancer cells.

Uniform polypyrrole (PPy) nanoparticles are fabricated from a facile one-step aqueous dispersion polymerization. Owing to their high photothermal conversion efficiency and photostability compared with the well-known Au nanorods, as well as their good colloidal stability and biocompatibility, the resulting PPy nanoparticles can used as a novel promising photothermal ablation coupling agent for targeted treatment of cancer.

Gold‐Nanoshelled Microcapsules: A Theranostic Agent for Ultrasound Contrast Imaging and Photothermal Therapy

The term theranostics, which is derived from “diagnostics” and “therapy”, refers to a treatment strategy that combines a diagnostic test and a specific therapy based on the test results. This integration of diagnostic imaging capability with therapy is critical in addressing the challenges of cancer heterogeneity and adaptation. Therefore, theranostic agents have received a great deal of recent research interest in cancer diagnosis and treatment. Among all the diagnostic imaging techniques, ultrasound imaging has a unique advantage because of its features of real-time, low-cost, high safety, and ease of incorporation into portable devices. With the use of ultrasound contrast agents (UCAs), the resolution and sensitivity of clinical ultrasound imaging have been greatly improved. Microcapsules composed of poly(lactic acid) (PLA), which has outstanding biocompatibility and biodegradability, show good ultrasound contrast-enhancing capabilities and other advantages: they have good mechanical strength and are thus stable, they can load either hydrophilic or hydrophobic species or both, and they are surface-charged and have functional groups on the surface so that they could be easily modified to introduce further practical features. Gold nanostructures exhibit good biocompatibility as well as excellent optical and electronic properties, thus allowing use in biological and medical applications. Gold nanoshells have a spherical dielectric core particle surrounded by a thin nanoscale gold shell. By controlling the thickness of the gold shell and the diameter of the core, the plasmon resonance and the resulting optical absorption of gold nanoshells can be tuned to the near-infrared (NIR) region, where the absorption of human tissues is minimal and penetration is optimal. On the other hand, the strong optical absorption of nanoshells can rapidly increase the local temperature under NIR irradiation. Therefore, the gold nanoshells can be used as photoabsorbers for remote NIR photothermal ablation therapy. Lasers and photoabsorbers such as gold nanostructures are used to carry out cancer treatment in photothermal therapy. However, the location and size of cancers must be identified before therapy, the treatment procedure needs to be monitored in real time during therapy, and the effectiveness has to be assessed after therapy. Contrast-enhanced ultrasound imaging could be the technique of choice to address these tasks. Therefore, the development of goldnanoshell-based UCAs could operate as a multifunctional theranostic agent for imaging-guided photothermal therapy. We have developed a novel multifunctional theranostic agent based on gold-nanoshelled microcapsules (GNS-MCs) by electrostatic adsorption of gold nanoparticles as seeds onto the polymeric microcapsule surfaces, followed by the formation of gold nanoshells by using a surface seeding method (Figure 1). The polymeric microcapsules were generated from PLA and polyvinyl alcohol (PVA) materials by employing the water-in-oil-in-water (W/O/W) double-emulsion method, and were negatively charged with a zeta potential of about 25 mV. Upon exposure to positively charged poly(allyl-

Glucose biosensor based on nanocomposite films of CdTe quantum dots and glucose oxidase.

A blood glucose sensor has been developed based on the multilayer films of CdTe semiconductor quantum dots (QDs) and glucose oxidase (GOD) by using the layer-by-layer assembly technique. When the composite films were contacted with glucose solution, the photoluminescence of QDs in the films was quickly quenched because the enzyme-catalyzed reaction product (H2O2) of GOD and glucose gave rise to the formation of surface defects on QDs. The quenching rate was a function of the concentration of glucose. The linear range and sensitivity for glucose determination could be adjusted by controlling the layers of QDs and GOD. The biosensor was used to successfully determine the concentration of blood glucose in real serum samples without sample pretreatment and exhibited satisfactory reproducibility and accuracy.

Prussian blue nanoparticles operate as a new generation of photothermal ablation agents for cancer therapy

Herein, prussian blue nanoparticles, an ancient dye, were explored as a new generation of near-infrared laser-driven photothermal ablation agents for cancer therapy alternative to traditional agents due to their good photothermal efficiency and high photothermal stability but low cost and particularly clinically approved biosafety.

Theranostic porphyrin dyad nanoparticles for magnetic resonance imaging guided photodynamic therapy.

Photodynamic therapy (PDT) is a site-specific treatment of cancer involving the administration of a photosensitizer (PS) followed by the local light activation. Besides efficient PSs, image guidance is essential for precise and safe light delivery to the targeting site, thus improving the therapeutic effectiveness. Herein, we report the fabrication of theranostic porphyrin dyad nanoparticles (TPD NPs) for magnetic resonance imaging (MRI)-guided PDT cancer therapy, where the inner metal free porphyrin functions as a photosensitizer for PDT while the outer Mn-porphyrin serve as an MRI contrast agent. Covalent attachment of porphyrins to TPD NPs avoids premature release during systemic circulation. In addition, TPD NPs (~60 nm) could passively accumulate in tumors and be avidly taken up by tumor cells. The PDT and MRI capabilities of TPD NPs can be conveniently modulated by varying the molar ratio of metal free porphyrin/Mn-porphyrin. At the optimal molar ratio of 40.1%, the total drug loading content is up to 49.8%, 31.3% for metal free porphyrin and 18.5% for Mn-porphyrin. The laser light ablated the tumor completely within 7 days in the presence of TPD NPs and the tumor growth inhibition was 100%. The relaxivities were determined to be 20.58 s(-1) mm(-1) for TPD NPs, about four times as much as that of Mn-porphyrin (5.16 s(-1) mm(-1)). After 24 h intravenous injection of TPD NPs, MRI images showed that the whole tumor area remained much brighter than surrounding healthy tissue, allowing to guide the laser light to the desired tumor site for photodynamic ablation.

Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy.

Imaging guided photothermal therapy using iron oxide loaded poly(lactic acid) microcapsules coated with graphene oxide

A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.

Novel iron–polysaccharide multilayered microcapsules for controlled insulin release

Iron-polysaccharide complexes have been extensively used for the treatment of iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe(3+) and dextran sulfate (DS) onto the surface of insulin microparticles. Fe(3+) was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe(3+)/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe(3+)/DS)(n) multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56+/-0.97% and drug loading content of 46.15+/-0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe(3+) as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.

Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer

This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.

Cerasomal doxorubicin with long-term storage stability and controllable sustained release

Liposomal nanohybrid cerasomes display a remarkable ability to maintain their size and retain encapsulated doxorubicin (DOX) over a period of 90days under storage conditions in solution compared with liposomes and liposils. Cerasomes retained 92.1±2.9% of the drug payload after 90days storage, much more than liposomes (35.2±2.5%) and liposils (53.2±5.5%). Under physiologically relevant conditions cerasomes exhibit a low initial burst in the first 5h and subsequent sustained release of DOX over the next 150h. Moreover, the magnitude of the initial burst and the rate of sustained release of DOX from cerasomes can be modulated by incorporating dipalmitoylphosphatidylglycerol (DPPG) in the cerasome structure and altering the ratios of the cerasome-forming lipid and phospholipids. Consequently, a wide range of release profiles can be achieved by altering the vesicle composition. Finally, human ovarian cancer cells are effectively killed by DOX released from cerasomes. Together these results suggest that cerasomes may be a promising drug delivery system for the long-term storage and controllable sustained release of the anticancer drug DOX.