Ye Wang

Drug-releasing implants: current progress, challenges and perspectives

The need for more efficient drug delivery strategies to treat resilient diseases and the rise of micro and nanotechnology have led to the development of more sophisticated drug-releasing implants with improved capabilities and performances for localised and controlled therapies. In recent years, implantable drug-releasing systems have emerged as an outstanding alternative to conventional clinical therapies. This new breed of implants has shown promising capabilities to overcome the inherent problems of conventional implants and therapies, making clinical treatments more efficient with minimal side effects. Recent clinical trials have demonstrated that this technology can improve the life of patients and increase their life expectancy. Within this context, this review is aimed at highlighting the different types and concepts of drug-releasing implants incorporating new nanomaterials and nanotechnology-based devices. Furthermore, the principles on which these drug-releasing implants are based as well as their advantages and limitations are discussed in detail. Finally, we provide a future perspective in the development of implantable clinical drug-delivery systems based on micro and nanotechnology.

Structurally engineered anodic alumina nanotubes as nano-carriers for delivery of anticancer therapeutics.

Here, we report a study on the biocompatibility, cell uptake and inxa0vitro delivery of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) by new nano-carriers called anodic alumina nanotubes (AANTs) for potential cancer therapy. AANTs were electrochemically engineered by a unique pulse anodization process, which enables precise control of the nanotube geometry, and used here as nano-carriers for drug delivery. Inxa0vitro cytotoxicity and cell uptake of AANTs was assessed using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells. AANTs exhibited excellent biocompatibility in both cell lines over a time course of five days even at a maximum concentration of AANTs of 100xa0μgmL(-1). Transmission electron microscopy and fluorescence microscopy confirmed a significant uptake of AANTs by RAW 264.7xa0cells and breast cancer cells. AANTs loaded with the pro-apoptotic protein Apo2L/TRAIL showed exceptional loading capacity (104xa0±xa014.4xa0μgmg(-1) of AANTs) and demonstrated significant decrease in viability of MDA-MB231-TXSA cancer cells due to apoptosis induction. These results demonstrate that AANTs are promising nano-carriers for drug delivery applications.

An overview of nanotoxicity and nanomedicine research: principles, progress and implications for cancer therapy

The toxic paradigms of chemotherapeutic drugs and nanoparticles are tightly linked. Whereas uncontrolled exposure of living systems to therapeutics/nanomaterials leads to toxicity, selective induction of cytotoxicity in cancer cells helps in the fight against cancer. The increasing understanding of nanotoxicity paradigms has recently resulted in important benchmarks for the safe design of nanomaterial-based drug delivery systems aiming to fight cancer. In this context, this review aims to compile and present recent advances, outcomes and interconnections between nanomaterial-based drug delivery and nanotoxicity disciplines in order to provide a comprehensive guidance for future research. First, the basic concepts and mechanisms of nanomaterial-based drug delivery and nanotoxicity are introduced. Second, we present a detailed classification of drug delivery strategies and nanotoxicity paradigms, supported by the most recent research studies with a special focus on the interconnections between nanotoxicity and drug delivery research, which are highlighted in order to explore future opportunities for developing advanced therapeutic approaches. Finally, this review is concluded with future prospects on the use of nanoparticles for manipulating the behavior of cells and animals.

Biomimetic Nanoporous Anodic Alumina Distributed Bragg Reflectors in the Form of Films and Microsized Particles for Sensing Applications

In this study, we produce for the first time biomimetic films and microsized particles based on nanoporous anodic alumina distributed Bragg reflectors (NAA-DBRs) by a rational galvanostatic pulse-anodization approach. These biomimetic photonic structures can feature a broad range of vivid bright colors, which can be tuned across the UV-visible spectrum by engineering their nanoporous structure through different anodization parameters. The effective medium of NAA-DBRs films is systematically assessed as a function of the anodization period, the anodization temperature, and the current density ratio by reflectometric interference spectroscopy (RIfS). This analysis makes it possible to establish the most sensitive structure toward changes in its effective medium. Subsequently, specific detection of vitamin C molecules is demonstrated. The obtained results reveal that NAA-DBRs with optimized structure can achieve a low limit of detection for vitamin C molecules as low as 20 nM, a sensitivity of 227±4 nm μM(-1), and a linearity of 0.9985. Finally, as proof of concept, we developed a new photonic nanomaterial based on NAA-DBR microsized particles, which could provide new opportunities to produce microsized photonic analytical tools.

Systematic in vitro nanotoxicity study on anodic alumina nanotubes with engineered aspect ratio: Understanding nanotoxicity by a nanomaterial model

Here, we report a detailed and systematic approach for studying the inxa0vitro nanotoxicity study of high aspect ratio (HAR) nanomaterials using anodic alumina nanotubes (AANTs) as a nanomaterial model. AANTs with bio-inert properties and tailored aspect ratios ranging from 7.8 to 63.3 were synthesized by an electrochemical pulse anodization process. Cytotoxicity studies were conducted with RAW 264.7 mouse macrophage cells and MDA-MB 231-TXSA human breast cancer cells through several toxicity parameters, including cell viability and morphology, pro-inflammatory response, mitochondrial depolarization, lysosomal membrane permeabilization (LMP), induction of autophagy and endoplasmic reticulum (ER) stress. The resulting toxicity patterns were cell-type dependent and strongly related with AANTs dose, length of time, and importantly the AR of AANTs. Long AANTs triggered enhanced cell death, morphological changes, tumor necrosis factor α (TNF-α) release, LMP and ER stress than short AANTs. The toxic AR window of AANTs was determined to be 7.8, which is shorter than that of other previously reported HAR nanomaterials. This toxic AR window provides a promising opportunity to control the nanotoxicity of HAR nanomaterials for their advanced drug delivery application.

Facile synthesis of optical microcavities by a rationally designed anodization approach: tailoring photonic signals by nanopore structure.

Structural engineering of porous anodic aluminum oxide (AAO) nanostructures by anodization has been extensively studied in the past two decades. However, the transition of this technique into the fabrication of AAO-based one-dimensional photonic crystal is still challenging. Herein, we report for the first time on the fabrication of AAO optical microcavities by a rationally designed anodization approach. In our study, two feasible methods are used to fabricate microcavities with tunable resonance peak across the visible and near-infrared spectra. Distributed Bragg reflector (DBR) nanostructures are first fabricated by pulse anodization approach, in which the anodization voltage was periodically manipulated to achieve pseudosinusoidal modulation of the effective refractive index gradient along the depth of the AAO nanostructures. Microcavities were created by creating a nanoporous layer of constant porosity between two AAO-DBR nanostructures, and by introducing a shift of the phase of the porosity gradient along the depth of AAO. The position of the resonance peak in these microcavities can be linearly tuned by means of the duration of the high voltage anodization. These optical nanostructures are sensitive to alterations of the effective media inside the nanopores. The AAO microcavity shows a central wavelength shift of 2.58 ± 0.37 nm when exposed to water vapor. Our research highlights the feasibility of anodization technique to fabricate AAO-based photonic nanostructures for advanced sensing applications.

Rational design of photonic dust from nanoporous anodic alumina films: a versatile photonic nanotool for visual sensing

Herein, we present a systematic study on the development, optimisation and applicability of interferometrically coloured distributed Bragg reflectors based on nanoporous anodic alumina (NAA-DBRs) in the form of films and nanoporous microparticles as visual/colorimetric analytical tools. Firstly, we synthesise a complete palette of NAA-DBRs by galvanostatic pulse anodisation approach, in which the current density is altered in a periodic fashion in order to engineer the effective medium of the resulting photonic films in depth. NAA-DBR photonic films feature vivid colours that can be tuned across the UV-visible-NIR spectrum by structural engineering. Secondly, the effective medium of the resulting photonic films is assessed systematically by visual analysis and reflectometric interference spectroscopy (RIfS) in order to establish the most optimal nanoporous platforms to develop visual/colorimetric tools. Then, we demonstrate the applicability of NAA-DBR photonic films as a chemically selective sensing platform for visual detection of mercury(II) ions. Finally, we generate a new nanomaterial, so-called photonic dust, by breaking down NAA-DBRs films into nanoporous microparticles. The resulting microparticles (μP-NAA-DBRs) display vivid colours and are sensitive towards changes in their effective medium, opening new opportunities for developing advanced photonic nanotools for a broad range of applications.

Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy.

Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs-induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy.

Titanium wire implants with nanotube arrays: A study model for localized cancer treatment

Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach. Previously, we reported the design and fabrication of nano-engineered 3D titanium wire based implants with titania (TiO2) nanotube arrays (Ti-TNTs) for applications such as bone integration by using in-vitro culture systems. The aim of present study is to demonstrate the feasibility of using such Ti-TNTs loaded with anti-cancer agent for localized cancer therapy using pre-clinical cancer models and to test local drug delivery efficiency and anti-tumour efficacy within the tumour environment. TNF-related apoptosis-inducing ligand (TRAIL) which has proven anti-cancer properties was selected as the model drug for therapeutic delivery by Ti-TNTs. Our in-vitro 2D and 3D cell culture studies demonstrated a significant decrease in breast cancer cell viability upon incubation with TRAIL loaded Ti-TNT implants (TRAIL-TNTs). Subcutaneous tumour xenografts were established to test TRAIL-TNTs implant performance in the tumour environment by monitoring the changes in tumour burden over a selected time course. TRAIL-TNTs showed a significant regression in tumour burden within the first three days of implant insertion at the tumour site. Based on current experimental findings these Ti-TNTs wire implants have shown promising capacity to load and deliver anti-cancer agents maintaining their efficacy for cancer treatment.

Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic

Iron oxide nanowires produced by bacteria (Mariprofundus ferrooxydans) are demonstrated as new multifunctional drug carriers for triggered therapeutics release and cancer hyperthmia applications. Iron oxide nanowires are obtained from biofilm waste in the bore system used to pump saline groundwater into the River Murray, South Australia (Australia) and processed into individual nanowires with extensive magnetic properties. The drug carrier capabilities of these iron oxide nanowires (Bac-FeOxNWs) are assessed by loading anticancer drug (doxorubicin, Dox) followed by measuring its elution under sustained and triggered release conditions using alternating magnetic field (AMF). The cytotoxicity of Bac-FeOxNWs assessed in 2D (96 well plate) and 3D (Matrigel) cell cultures using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells shows that these Bac-FeOxNWs are biocompatible even at concentrations as high as 250 μg/mL after 24 h of incubation. Finally, we demonstrate the capabilities of Bac-FeOxNWs as potential hyperthermia agent in 3D culture setup. Application of AMF increased the local temperature by 14 °C resulting in approximately 34% decrease in cell viability. Our results demonstrate that these naturally produced nanowires in the form of biofilm can efficiently act as drug carriers with triggered payload release and magnetothermal heating features for potential anticancer therapeutics applications.