Shang-Hsiu Hu

Quantum-Dot-Tagged Reduced Graphene Oxide Nanocomposites for Bright Fluorescence Bioimaging and Photothermal Therapy Monitored In Situ

Quantum-dot-tagged reduced graphene oxide (QD-rGO) nanocomposites (left) internalized into targeted tumor cells display bright fluorescence from the QDs (right); by absorbing NIR radiation incident on the rGO and converting it into heat, they also cause simultaneous cell death and fluorescence reduction (bottom). The nanocomposite is thus capable of tumor imaging, photothermal therapy and in situ monitoring of treatment in progress.

Controlled Rupture of Magnetic Polyelectrolyte Microcapsules for Drug Delivery

In this study, a magnetic-sensitive microcapsule was prepared using Fe 3O 4/poly(allylamine) (Fe 3O 4/PAH) polyelectrolyte to construct the shell. Structural integrity, microstructural evolution, and corresponding release behaviors of fluorescence dyes and doxorubicin were systematically investigated. Experimental observations showed that the presence of the magnetic nanoparticles in the shell structure allowed the shell structure to evolve from nanocavity development to final rupture of the shell under a given magnetic stimulus of different time durations. Such a microstructural evolution of the magnetic sensitive shell structure explained a corresponding variation of the drug release profile, from relatively slow release to burst-like behavior at different stages of stimulus. It has proposed that the presence of magnetic nanoparticles produced heat, due to magnetic energy dissipation (as Brown and Neel relaxations), and mechanical vibration and motion that induced stress development in the thin shell. Both mechanisms significantly accelerated the relaxation of the shell structure, causing such a microstructural evolution. With such a controllable microstructural evolution of the magnetic-sensitive shell structure, active substances can be well-regulated in a manageable manner with a designable profile according to the time duration under magnetic field. A cell culture study also indicated that the magnetic-sensitive microcapsules allowed a rapid uptake by the A549 cell line, a cancerous cell line, suggesting that the magnetic-sensitive microcapsule with controllable rupturing behavior of the shell offers a potential and effective drug carrier for anticancer applications.

Core/Single‐Crystal‐Shell Nanospheres for Controlled Drug Release via a Magnetically Triggered Rupturing Mechanism

Core/single-crystal-shell nanospheres are constructed from a poly-(N-vinyl- 2-pyrrolidone) (PVP)-modified silica core with an outer layer of single-crystal iron oxide shell. The nanospheres show outstanding release-and-zero-release characteristics via the addition and removal, respectively, of an external high-frequency magnetic field.

Instantaneous Drug Delivery of Magnetic/Thermally Sensitive Nanospheres by a High-Frequency Magnetic Field

Novel dual-functional nanospheres composed of magnetic iron oxide nanoparticles embedded in a thermo-sensitive Pluronic F127 (F127) matrix were successfully synthesized by an in situ coprecipitation process. The nanospheres were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Experimental observations indicated that the F127 was subjected to a rapid structural change when the magnetic phase caused rapid heating after a short exposure to a high-frequency magnetic field. During the field duration, considerable volume shrinkage of the nanospheres (2.3-fold diameter reduction) was detected. This has been translated to an instantaneous release of a drug, Doxorubicin (DOX), when the DOX was encapsulated within the nanospheres. Such a rapidly responsive release of the DOX from the nanospheres was due to an intimate contact between the nanomagnet and F127, where an effective thermal and mechanical transfer between core and shell phases efficiently took place in the presence of the magnetic field.

Core‐Shell Nanocapsules Stabilized by Single‐Component Polymer and Nanoparticles for Magneto‐Chemotherapy/Hyperthermia with Multiple Drugs

Iron-oxide-containing double emulsion capsules carrying both hydrophilic and hydrophobic therapeutic molecules can deliver drugs and energy on demand in vivo. Magneto-chemotherapy/hyperthermia involves a burst-like release of hydrophilic doxorubicin and hydrophobic paclitaxel, remotely triggered by a high frequency magnetic field, which also releases energy via internalized iron oxide nanoparticles, all contributing to cell kill.

Multifunctional magnetically removable nanogated lids of Fe3O4–capped mesoporous silica nanoparticles for intracellular controlled release and MR imaging

In this study, a novel nanocarrier (MSN@Fe3O4) is constructed using a facile technology by capping mesoporous silica nanoparticles (MSN) with monodispersed Fe3O4 nanoparticles through chemical bonding. The chemical links provide adhesion, which permits the magnetic nanoparticles, as nano-caps, to efficiently cover the mesoporous pores on the mesoporous silica matrix and be tightly bonded with the matrix surface. Without magnetic stimulus, none or only a negligible amount of the drug can be released from the MSN@Fe3O4. However, when subjected to an external controllable magnetic field, a quantity of nano-caps can be remotely and precisely removed, giving tunable release profiles for an anticancer drug, (S)-(+)-camptothecin (CPT), with various dosages depending upon the strength and time period of magnetic induction. The transverse relaxivity (r2) of the MSN@Fe3O4 nanocarriers was measured to be about 121.57 s−1mM−1Fe, which is larger than that for the reported mesoporous silica nanoparticles decorated with magnetite nanocrystals. Therefore, MSN@Fe3O4 nanocarriers could perform well as T2- type MR contrast enhancement agents for cell or molecular imaging. In addition, the MSN@Fe3O4 nanocarriers also demonstrate fairly high cell uptake efficiency. Together with its versatile magnetic manipulation, this new type of MSN@Fe3O4 nanosystem can be considered as a new class of multifunctional nanodevice, with combined tunable drug release and nanoimaging modalities for a variety of biomedical uses.

Functionalized graphene nanocomposites for enhancing photothermal therapy in tumor treatment

Graphene and its derivatives have unique physical and chemical properties that make them promising vehicles for photothermal therapy (PTT)-based cancer treatment. With intrinsic near-infrared (NIR) absorption properties, graphene-based nanomaterials can be used for PTT and other therapeutics, particularly in combination therapy, to provide successful thermal ablation of cancer cells. In the recent years, advances in graphene-based PTT have produced efficient and efficacious tumor inhibition via nanomaterial structural design and different functionalizations of graphene-derived nanocomposites. Graphene-based nanosystems exhibit multifunctional properties that are useful for PTT applications including enhancement of multimodalities, guided imaging, enhanced chemotherapy and low-power efficient PTT for optimum therapeutic efficiency. Therefore, in this review, we address critical issues and future aspects of PTT-based combination therapy.

Characterization and drug release behavior of highly responsive chip-like electrically modulated reduced graphene oxide-poly(vinyl alcohol) membranes

Hybrid hydrogel membranes composed of reduced graphene oxide (rGO) nanosheets and a poly (vinyl alcohol) (PVA) matrix were investigated as an electrically responsive drug release system. The rGO nanosheets in the matrix act as a physical barrier to inhibit the release of the model anesthetic drug, lidocaine hydrochloride, but the highly responsive release can be enhanced by the presence of rGO when exposed to an electrical stimulus. More interestingly, the on-demand drug release profiles of the assembled rGO–PVA hydrogel into a chip-like device can be highly controlled by an external electrical field. Release profiles ranging from a slow-elution pattern to a rapid release under electrical field treatment can be achieved by manipulating the rGO–PVA composition. Moreover, under cyclic exposure to an electrical stimulus, a highly controllable and repeatedly pulsatile release with desirable precision is obtained from the rGO–PVA hydrogel, implying that the hydrogel exhibits excellent anti-fatigue properties. By combining with the enhanced structural integrity and biocompatibility, the electrically responsive rGO–PVA hydrogel has demonstrated potential biological applications in drug delivery systems. In addition, the easy loading of hydrophilic drugs into the rGO–PVA hydrogel opens up a promising future in biological applications, such as transdermal therapy and wound healing.

Magnetic core-shell nanocapsules with dual-targeting capabilities and co-delivery of multiple drugs to treat brain gliomas.

Lactoferrin (Lf)-tethered magnetic double emulsion nanocapsules (Lf-MDCs) are assembled from polyvinyl alcohol (PVA), polyacrylic acid (PAA), and iron oxide (IO) nanoparticles. The core-shell nanostructure of the Lf-MDCs (particle diameters from 100 to 150 nm) can simultaneously accommodate a hydrophilic drug, doxorubicin (Dox), and a hydrophobic drug, curcumin (Cur), in the core and shell, respectively, of the nanocapsules for an efficient drug delivery system. The release patterns of the two drugs can be regulated by manipulating the surface charges and drug-loading ratios, providing the capability for a stepwise adjuvant release to treat cancer cells. The results demonstrate that the dual (Dox+Cur)-drug-loaded nanocapsule can be effectively delivered into RG2 glioma cells to enhance the cytotoxicity against the cells through a synergistic effect. The combined targeting, i.e., magnetic guidance and incorporation of Lf ligands, of these Lf-MDCs results in significantly elevated cellular uptake in the RG2 cells that overexpress the Lf receptor. Interestingly, an intravenous injection of the co-delivered chemotherapeutics follows by magnetic targeting in brain tumor-bearing mice not only achieve high accumulation at the targeted site but also more efficiently suppress cancer growth in vivo than does the delivery of either drug alone.

SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy.

Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r2 value can be enhanced from 164 to 208 (s(-1)mM (-1)Fe) by increasing the SPIO concentration from 14.1 to 28.2mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy.