Synthesis of nanomedicines by nanohybrids conjugating ginsenosides with auto-targeting and enhanced MRI contrast for liver cancer therapy

A new methodology has been developed with conjugating nanoparticles (NPs) with an active ingredient of Chinese herbs for nanomedicines with auto-targeting and enhanced magnetic resonance imaging (MRI) for liver cancer therapy. Fe@Fe₃O₄ NPs are first synthesized via the programed microfluidic process, whose surfaces are first modified with –NH₂ groups using a silane coupling technique that uses (3-aminopropyl)trimethoxysilane (APTMS) as the coupling reagent and are subsequently activated by the bifunctional amine-active cross-linker [e.g. disuccinimidyl suberate (DSS)]. The model medicines of ginsenosides pre-activated by APTMS are further cross-linked with activated NPs, forming the desired nanomedicines (Nano-Fe-GSS). Sizes and structures of Fe@Fe₃O₄ NPs were characterized by transmission electron microscopy and X-ray diffraction, revealing that their core-shell structures consist of amorphous boron doped Fe cores and partial crystalline Fe₃O₄ shells. The accomplishment of coupling reactions in the final nanomedicines is confirmed by the characterization of the composition of NPs and Nano-Fe-GSS via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. The nanoparticles’ effects as MRI contrast agents are further investigated by comparing the T₂ weighted spin echo imaging (T2WI) in livers before and after intravenous injection and intragastric administration of nanomedicines. The results indicate that these nanomedicines possess enhanced MRI effects. Investigation of the toxicity and metabolism of Nano-Fe-GSS suggests that they are safe to related vital organs. The results provide an efficient alternative route to synthesize desired multi-functional nanomedicines based on NPs and the active ingredients of Chinese herbs, which can promote their potential synergistic effects in anti-tumor therapy.     

Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe₂O₄ nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.     

Multifunctional Magnetic-fluorescent Nanocomposites for Biomedical Applications

Nanotechnology is a fast-growing area, involving the fabrication and use of nano-sized materials and devices. Various nanocomposite materials play a number of important roles in modern science and technology. Magnetic and fluorescent inorganic nanoparticles are of particular importance due to their broad range of potential applications. It is expected that the combination of magnetic and fluorescent properties in one nanocomposite would enable the engineering of unique multifunctional nanoscale devices, which could be manipulated using external magnetic fields. The aim of this review is to present an overview of bimodal “two-in-one” magnetic-fluorescent nanocomposite materials which combine both magnetic and fluorescent properties in one entity, in particular those with potential applications in biotechnology and nanomedicine. There is a great necessity for the development of these multifunctional nanocomposites, but there are some difficulties and challenges to overcome in their fabrication such as quenching of the fluorescent entity by the magnetic core. Fluorescent-magnetic nanocomposites include a variety of materials including silica-based, dye-functionalised magnetic nanoparticles and quantum dots-magnetic nanoparticle composites. The classification and main synthesis strategies, along with approaches for the fabrication of fluorescent-magnetic nanocomposites, are considered. The current and potential biomedical uses, including biological imaging, cell tracking, magnetic bioseparation, nanomedicine and bio- and chemo-sensoring, of magnetic-fluorescent nanocomposites are also discussed.     

Cytocompatible and multifunctional polymeric nanoparticles for transportation of bioactive molecules into and within cells

Multifunctional polymeric nanoparticles are materials with great potential for a wide range of biomedical applications. For progression in this area of research, unfavorable interactions of these nanoparticles with proteins and cells must be avoided in biological environments, for example, through treatment of the nanoparticle surfaces. Construction of an artificial cell membrane structure based on polymers bearing the zwitterionic phosphorylcholine group can prevent biological reactions at the surface effectively. In addition, certain bioactive molecules can be immobilized on the surface of the polymer to generate enough affinity to capture target biomolecules. Furthermore, entrapment of inorganic nanoparticles inside polymeric matrices enhances the nanoparticle functionality significantly. This review summarizes the preparation and characterization of cytocompatible and multifunctional polymeric nanoparticles; it analyzes the efficiency of their fluorescence function, the nature of the artificial cell membrane structure, and their performance as in-cell devices; and finally, it evaluates both their chemical reactivity and effects in cells.     

Water-soluble fullerenes for medical applications

Research on fullerenes occupies a unique position in the scientific arena. Synthesis and characterisation of this nanomaterial blur the line between materials science and chemistry; careful tuning of the processing methods gives birth to a whole family of molecules and their functionalised derivatives, whose unusual properties at this nanoscopic scale can be exploited in cutting-edge technological applications. This review focuses on the functionalisation of fullerenes for use in medical applications. The first half gives an introduction to the fullerenes themselves and how their fundamental properties lead to a very rich chemistry, enabling both exohedral (external) and endohedral (internal) functionalisations of the cage. Emphasis is placed on the need for safe and reproducible synthesis routes if fullerenes are ever going to make it to the pharmaceutical market. In line with this, a selection of exohedral functionalisation protocols receives particular attention. Coverage of endohedral fullerene synthesis routes is limited to the endohedral metallofullerenes. In the second half, myriad applications of fullerenes in biomedical contexts are introduced and certain synthesis routes are critically evaluated. Discussion of the need to water solubilise the hydrophobic fullerene cages precedes an overview of fullerene-based diagnostic and therapeutic technologies. A final moment is spent on toxicity studies of fullerenes. The concluding remarks emphasise the positive effects of incorporating fullerenes into biomedical technologies, while looking at how these are perceived by the general public. A case is made for fullerenes being the optimal choice as standard bearers in the advance of nanomaterials into the medical field.

This is the winning review of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining, run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged.     

Mixed oxide nanotubes in nanomedicine: A dead-end or a bridge to the future?

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide nanotubes (MONs) and their potential applications, especially in biomedical applications are still in the early stages of development. This review aims to establish a credible platform for the current and future roles of MONs in nanomedicine, particularly in advanced orthopedic implants. We first introduce the concept of MONs and then discuss the preparation strategies. This is followed by a review of the recent advancement of MONs in biomedical applications, including mineralization abilities, biocompatibility, antibacterial activity, cell culture, and animal testing, as well as clinical possibilities. To conclude, we propose that the combination of nanotubular surface modification with incorporating sensor allows clinicians to precisely record patient data as a critical contributor to evidence-based medicine.     

Dual stimuli-responsive polymeric hollow nanocapsules as “smart” drug delivery system against cancer

ABSTRACT

Novel thermal- and pH-responsive hollow nanocapsules (HNCaps) were fabricated through the grafting of a thiol-end capped PNIPAAm-b-PAA by thiol-ene “click” reaction onto PMMA HNCaps. The lowest critical solution temperature (LCST) of the fabricated HNCaps was obtained as 38–40°C. The fabricated nanosystem was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies were obtained as 62 and 53%, respectively. The in vitro stimuli-responsive drug release behavior of the fabricated nanomedicine was investigated extensively. The anticancer activity of the drug-loaded HNCaps was evaluated using MTT assay against MCF7 cells. The results exhibited excellent potential of nanosystem as a drug delivery system (DDS) for cancer chemotherapy.     

Quantum Dots in Biological and Biomedical Research: Recent Progress and Present Challenges

The marriage of nanomaterials with biology has produced a new generation of technologies that can profoundly impact biological and biomedical research. Quantum dots (Qdots) are an archetype for this hybrid research area and have gained popularity and interest from diverse research communities because of their unique and tunable optical properties. In this Review, we will describe their history and development, optical and electronic properties, and applications in biology and medicine. A critical evaluation of barriers impacting current Qdot technologies will be discussed and insights into the future outlook of the field will be explored.     

Modeling of retrograde nanoparticle transport in axons and dendrites

This paper presents a pioneering modeling study on nanoparticle internalization and transport in neurons. The model developed in this paper is based on recent experimental results that indicate that after entering a neurite by endocytosis, nanoparticles are transported toward the neuron soma in endocytic vesicles by retrograde molecular-motor-driven transport. Experimental results also indicate that nanoparticles enter axons at axon terminals while in dendrites they enter through the entire plasma membrane. The model equations developed in this paper are based on these experimental observations. The analytical solution of these equations is obtained; the solution predicts the distribution of the concentration of nanoparticles associated with free nanoparticle-loaded vesicles (NLVs) (not transported on microtubules (MTs)) as well as the distribution of the concentration of nanoparticles associated with NLVs transported on MTs by dynein motors. The fluxes of nanoparticles by diffusion and motor-driven transport as well as the total (combined) flux of nanoparticles are also predicted.     

A Smart Nanotherapeutic Agent for in vitro and in vivo Reversal of Heavy-Metal-Induced Causality: Key Information from Optical Spectroscopy

Human exposure to heavy metals can cause a variety of life-threatening disorders, affecting almost every organ of the body, including the nervous, circulatory, cardiac, excretory, and hepatic systems. The presence of heavy metal (cause) and induced oxidative stress (effect) are both responsible for the observed toxic effects. The conventional and effective way to combat heavy metal overload diseases is through use of metal chelators. However, they possess several side effects and most importantly they fail to manage the entire causality. In this study, we introduce citrate-functionalized Mn₃O₄ nanoparticles (C−Mn₃O₄ NPs) as an efficient chelating agent for treatment of heavy metal overload diseases. By means of UV/Vis absorbance and steady-state fluorescence spectroscopic techniques we investigated the efficacy of the NPs in chelation of a model heavy metal, lead (Pb). We also explored the retention of antioxidant properties of the Pb-chelated C−Mn₃O₄ NPs using a UV/Vis-assisted DPPH assay. Through CD spectroscopic studies we established that the NPs can reverse the Pb-induced structural modifications of biological macromolecules. We also studied the in vivo efficacy of NPs in Pb-intoxicated C57BL/6j mice. The NPs were not only able to mobilize the Pb from various organs through chelation, but also saved the organs from oxidative damage. Thus, the C−Mn₃O₄ NPs could be an effective nanotherapeutic agent for complete reversal of heavy-metal-induced toxicity through chelation of the heavy metal and healing of the associated oxidative stress.