Design of magnetic nanoparticles-assisted drug delivery system

Magnetic nanoparticles (MNPs) have been designed for multifaceted applications such as contrast agents in magnetic resonance imaging (MRI) diagnosis, drug/gene carriers for different kinds of therapeutic agents, tissue repair, hyperthermia, immunoassay, and cell separation/sensing. This review highlights synthesis methods, stabilizers used for surface coating on MNPs, and target ligands for ferrying payloads to an interested disease area. Some of the recent biomedical applications of MNPs in the field of drug and DNA targeting delivery are extensively reviewed.     

Magnetism in drug delivery: The marvels of iron oxides and substituted ferrites nanoparticles

In modern drug delivery, seeking a drug delivery system (DDS) with a modifiable skeleton for proper targeting of loaded actives to specific sites in the body is of extreme importance for a successful therapy. Magnetically guided nanosystems, where particles such as iron oxides are guided to specific regions using an external magnetic field, can provide magnetic resonance imaging (MRI) while delivering a therapeutic payload at the same time, which represents a breakthrough in disease therapy and make MNPs excellent candidates for several biomedical applications. In this review, magnetic nanoparticles (MNPs) along with their distinguishable properties, including pharmacokinetics and toxicity, especially in cancer therapy will be discussed. The potential perspective of using other elements within the MNP system to reduce toxicity, improve pharmacokinetics, increase the magnetization ability, improve physical targeting precision and/or widen the scope of its biomedical application will be also discussed.     

Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging

Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties.     

Toward improved selectivity of targeted delivery: The potential of magnetic nanoparticles

Magnetic nanoparticles, mostly iron oxide-based nanoparticles, have long been used as contrasting agents in magnetic resonance imaging (MRI) applications, heat mediators in hyperthermia treatments and carriers for targeted drug delivery. Magnetic nanoparticles offer some attractive characteristics for targeted drug delivery such as drug carrying ability, nano-scale dimensions and magnetism-driven selective targeting. In this issue, Escribano et al. demonstrated that iron oxide-based magnetic nanoparticles with an implanted magnet can improve selective targeting to the site of inflammation. This result opens a promising avenue for magnetic drug targeting to inflammatory diseases.     

Magnetic nanoparticles: an update of application for drug delivery and possible toxic effects

Magnetic nanoparticles (MNPs) represent a subclass within the overall category of nanomaterials and are widely used in many applications, particularly in the biomedical sciences such as targeted delivery of drugs or genes, in magnetic resonance imaging, and in hyperthermia (treating tumors with heat). Although the potential benefits of MNPs are considerable, there is a distinct need to identify any potential toxicity associated with these MNPs. The potential of MNPs in drug delivery stems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of MNPs generated by different surface coatings. These surface modifications alter the particokinetics and toxicity of MNPs by changing protein–MNP or cell–MNP interactions. This review contains current advances in MNPs for drug delivery and their possible organ toxicities associated with disturbance in body iron homeostasis. The importance of protein–MNP interactions and various safety considerations relating to MNP exposure are also addressed.     

Emerging application of quantum dots for drug delivery and therapy

Quantum dots have proven themselves as powerful fluorescent probes, especially for long-term, multiplexed, and quantitative imaging and detection. Newly engineered quantum dots with integrated targeting, imaging and therapeutic functionalities have become excellent material to study drug delivery in cells and small animals. This fluorescent 'prototype' will provide important information in the rational design of biocompatible drug carriers and will serve as a superior alternative to magnetic and radioactive imaging contrast agents in preclinical drug screening, validation and delivery research. This Editorial article is not intended to offer a comprehensive review on drug delivery, but to highlight the breakthroughs in the emerging applications of quantum dots in this field and to provide our perspective on future research.     

Magnetically modulated therapeutic systems

Magnetically targeted drug delivery by particulate carriers is an efficient method of delivering drugs to localized disease sites, such as tumors. High concentrations of chemotherapeutic or radiological agents can be achieved near the target site without any toxic effects to normal surrounding tissue. Non-targeted applications of magnetic microspheres and nanospheres include their use as contrast agents (MRI) and as drug reservoirs that can be activated by a magnet applied outside the body. Historic and current applications of magnetic microspheres will be discussed, as well as future directions and problems to be overcome for the efficient and beneficial use of magnetic carriers in clinical practice. More information about the field and an extensive bibliography is available at "."     

超顺磁氧化铁纳米粒在药物传递系统中的研究进展

超顺磁氧化铁纳米粒作为一种新型纳米材料,不仅可用于临床磁共振成像对比剂,还可用于药物传递载体,近些年对它的研究和应用越来越受到人们的关注。本文从超顺磁氧化铁纳米粒的合成、表面修饰及其在药物传递中的应用进展情况做一综述。     

Inorganic nanomedicine—Part 1

Inorganic nanomedicine refers to the use of inorganic or hybrid nanomaterials and nanosized objects to achieve innovative medical breakthroughs for drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Potential uses for fluorescent quantum dots include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible quantum dot conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastatic cell tracking. Magnetic nanowires applications include biosensing and construction of nucleic acids sensors. Magnetic cell therapy is used for the repair of blood vessels. Magnetic nanoparticles (MNPs) are important for magnetic resonance imaging, drug delivery, cell labeling, and tracking. Superparamagnetic iron oxide nanoparticles are used for hyperthermic treatment of tumors. Multifunctional MNPs applications include drug and gene delivery, medical imaging, and targeted drug delivery. MNPs could have a vital role in developing techniques to simultaneously diagnose, monitor, and treat a wide range of common diseases and injuries.From the Clinical EditorThis review serves as an update about the current state of inorganic nanomedicine. The use of inorganic/hybrid nanomaterials and nanosized objects has already resulted in innovative medical breakthroughs for drug/gene discovery and delivery, discovery of biomarkers and molecular diagnostics, and is likely to remain one of the most prolific fields of nanomedicine.     

Magnetic iron oxide nanoparticles for tumor-targeted therapy

Magnetic nanoparticles have been intensively investigated due to their magnetic characteristics, quantum dot effects, as well as their potential applications in the area of bioscience and medicine. Very promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification which have been widely used experimentally for masses of in vivo applications such as magnetic resonance imaging contrast enhancement, drug delivery, and hyperthermia, etc.. All these biomedical applications require that these nanoparticles have effective magnetic values and suitable sizes. On the other hand, these applications need special surface modification of these particles, which not only have to be non-toxic and biocompatible, but also allow a targetable drug delivery in a specific area. This review summarizes the current research situation and development of magnetic iron oxide nanoparticles, and the biomedical applications ranging from drug delivery to hyperthermia for tumor-targeted therapy.     

Magnetic nanoparticles for theragnostics

Engineered magnetic nanoparticles (MNPs) represent a cutting-edge tool in medicine because they can be simultaneously functionalized and guided by a magnetic field. Use of MNPs has advanced magnetic resonance imaging (MRI), guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cell tracking and bioseparation. Integrative therapeutic and diagnostic (i.e., theragnostic) applications have emerged with MNP use, such as MRI-guided cell replacement therapy or MRI-based imaging of cancer-specific gene delivery. However, mounting evidence suggests that certain properties of nanoparticles (e.g., enhanced reactive area, ability to cross cell and tissue barriers, resistance to biodegradation) amplify their cytotoxic potential relative to molecular or bulk counterparts. Oxidative stress, a 3-tier paradigm of nanotoxicity, manifests in activation of reactive oxygen species (ROS) (tier I), followed by a proinflammatory response (tier II) and DNA damage leading to cellular apoptosis and mutagenesis (tier III). Invivo administered MNPs are quickly challenged by macrophages of the reticuloendothelial system (RES), resulting in not only neutralization of potential MNP toxicity but also reduced circulation time necessary for MNP efficacy. We discuss the role of MNP size, composition and surface chemistry in their intracellular uptake, biodistribution, macrophage recognition and cytotoxicity, and review current studies on MNP toxicity, caveats of nanotoxicity assessments and engineering strategies to optimize MNPs for biomedical use.     

Targeted multifunctional lipid-based nanocarriers for image-guided drug delivery

Lipid-based nanocarriers have proven successful in the delivery of mainly chemotherapeutic agents, and currently they are being applied clinically in the treatment of various types of cancer. These drug delivery systems achieve increased therapeutic efficacy by altering the pharmacokinetics and biodistribution of encapsulated drugs, resulting in decreased drug toxicity and enhanced accumulation in tumor tissue. This increased accumulation is due to the relatively leaky immature vasculature of a tumor. After the clinical relevance of such drug delivery systems was demonstrated, research in this area focused on optimization, both by cell specific targeting and including controlled and triggered release concepts within the carrier. These more advanced targeted nanocarriers in general have clearly shown their potential in various animal tumor models and await clinical application. The development of targeted nanocarriers in which therapeutic and imaging agents are merged into a single carrier will certainly be of importance in the near future. Indeed, scientists active in the field of imaging (e.g. nuclear and magnetic resonance imaging) have already started to exploit nanocarriers for molecular imaging. Image-guided drug delivery using these multifunctional nanocarriers, containing therapeutic and imaging agents, will ultimately allow for online monitoring of tumor location, tumor targeting levels, intratumoral localization and drug release kinetics prior and during radio- and/or chemotherapeutic treatment. This review describes the current status and challenges in the field of nanocarrier-aided drug delivery and drug targeting and discusses the opportunities of combining imaging probes with these drug carriers and the potential of these multifunctional lipid-based nanocarriers within image-guided drug delivery.     

Therapeutic applications of lipid-coated microbubbles

Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.     

Polysaccharide-based nanoparticles: a versatile platform for drug delivery and biomedical imaging

Polysaccharide-based nanoparticles have attracted interest as carriers for imaging and therapeutic agents because of their unique physicochemical properties, including biocompatibility and biodegradability. In addition, the functional groups of the polysaccharide backbone allow facile chemical modification to develop nanoparticles with diverse structures. Some polysaccharides have the intrinsic ability to recognize specific cell types, facilitating the design of targeted-drug delivery systems through receptor-mediated endocytosis. The main objective of this review is to provide an overview of various polysaccharide-based nanoparticles and to highlight the recent efforts that have been made to improve the characteristics of polysaccharide-based nanoparticles for drug delivery and biomedical imaging.     

Recent progress in dendrimer-based nanocarriers

A large number of drug delivery systems--mostly in the form of liposomes, microspheres, nanoparticles and hydrogels--have been designed to achieve targeted delivery and sustained release of drugs by exploiting the inherent properties of polymers. The size, shape, and surface properties of the polymer are used to modulate the pharmacokinetic and pharmacodynamic behavior of drugs conjugated with or encapsulated in the polymeric carrier. Recently, a class of well-defined, monodisperse, and tree-like polymers called dendrimers has attracted attention because of the flexibility they offer in terms of their size, shape, branching, length, and surface functionality. A unique characteristic of dendrimers is that they can act as a particulate system while retaining the properties of a polymer. Drugs and diagnostic agents can be encapsulated in the central core or bound to the surface of the dendrimer by noncovalent or covalent interaction. Dendritic polymers can significantly improve pharmacokinetic and pharmacodynamic properties of low molecular weight and protein-based therapeutic agents. Furthermore, fluorescent antibodies and imaging contrast agents can be bound to these new polymers and the resulting complexes can be used for analyzing biological fluids and for diagnosis. Because of their size, shape, and ability to conjugate with a wide range of chemical entities, dendrimers have found many applications in the pharmaceutical and biomedical sciences. This review focuses on the unique carrier properties of biomimetic dendrimers and discusses a wide range of applications of dendrimers in drug delivery, including their use as drug solubilizers, absorption enhancers, release modifiers, and carriers for targeting drugs and diagnostic agents.     

Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates

Recent progress in an emerging area of designing aptamer and nanomaterial conjugates as molecular diagnostic and drug delivery agents in biomedical applications is summarized. Aptamers specific for a wide range of targets are first introduced and compared to antibodies. Methods of integrating these aptamers with a variety of nanomaterials, such as gold nanoparticles, quantum dots, carbon nanotubes, and superparamagnetic iron oxide nanoparticles, each with unique optical, magnetic, and electrochemical properties, are reviewed. Applications of these systems as fluorescent, colorimetric, magnetic resonance imaging, and electrochemical sensors in medical diagnostics are given, along with new applications as smart drug delivery agents.     

Magnetic carriers: a promising device for targeting drugs into the human body

Suboptimal disposition behavior of drugs requires innovative delivery approaches. Magnetic drug targeting seems to be a promising one. Magnetic particles develop magnetic polarization and magnetophoretic mobility, and because of such unique properties, these carriers may be eligible candidates for delivering drugs to specific locations within the body. Their special properties also allow other uses, such as those in magnetic separation, hyperthermia, and magnetic resonance imaging. This review focuses on a brief discussion of magnetic drug targeting, the properties and fate of magnetic carriers, the methods used to produce and characterize them, and their other uses in biotechnology.     

磁性纳米粒子及其在生物医学中的应用进展

磁性纳米粒子由于独有的特性在医药中有着多种用途。其中最独特的特性是磁响应性,利用这一特性磁性粒子被应用于药物载体、磁性分离和细胞的分选。近年来由于其可作为对比剂用于磁共振成像、作为热疗介质用于癌症热疗,并且可应用于磁力组织工程而引起研究者们的广泛关注。具有独特特性的功能性纳米磁性粒子的这些应用将更进一步促进医药生物技术的发展。该综述主要介绍磁性纳米粒子在磁性分离与磁性转染、磁力组织工程、药物靶向载体、核磁共振、肿瘤热疗中的应用。     

Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides

Cell-penetrating peptides (CPPs) have been used to overcome the lipophilic barrier of the cellular membranes and deliver large molecules and even small particles inside the cell for their biological actions. CPPs are being used to deliver inside cell a large variety of cargoes such as proteins, DNA, antibodies, contrast (imaging) agents, toxins, and nanoparticular drug carriers including liposomes. In this paper, we have reviewed the delivery of different molecules and particles mediated by TAT, Antp, VP22, and other CPPs as well as potential applications of these delivery systems in different areas of vaccine development, cancer immunotherapy, gene delivery, and cellular imaging.