Showing papers on "Nanomedicine published in 2014"

Engineered Nanoparticles for Drug Delivery in Cancer Therapy

Abstract: In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.

Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery

Abstract: Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells This top-down engineering approach c

Nanotheranostics ˗ Application and Further Development of Nanomedicine Strategies for Advanced Theranostics

Abstract: Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage.

Targeted therapy using nanotechnology: focus on cancer.

Abstract: Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.

Abstract: Dendrimers are discrete nanostructures/nanoparticles with ‘onion skin-like’ branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as ‘generations’. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle–drug and nanoparticle–tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new ‘nanoperiodic’ concept which proposes nanoparticle structure control and the engineering of ‘critical nanoscale design parameters’ (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious and ocular diseases are reviewed. Finally we will consider challenges and opportunities anticipated for future clinical translation, nanotoxicology and the commercialization of nanomedicine.

Virus-Inspired Membrane Encapsulation of DNA Nanostructures To Achieve In Vivo Stability

Abstract: DNA nanotechnology enables engineering of molecular-scale devices with exquisite control over geometry and site-specific functionalization. This capability promises compelling advantages in advancing nanomedicine; nevertheless, instability in biological environments and innate immune activation remain as obstacles for in vivo application. Natural particle systems (i.e., viruses) have evolved mechanisms to maintain structural integrity and avoid immune recognition during infection, including encapsulation of their genome and protein capsid shell in a lipid envelope. Here we introduce virus-inspired enveloped DNA nanostructures as a design strategy for biomedical applications. Achieving a high yield of tightly wrapped unilamellar nanostructures, mimicking the morphology of enveloped virus particles, required precise control over the density of attached lipid conjugates and was achieved at 1 per ∼180 nm(2). Envelopment of DNA nanostructures in PEGylated lipid bilayers conferred protection against nuclease digestion. Immune activation was decreased 2 orders of magnitude below controls, and pharmacokinetic bioavailability improved by a factor of 17. By establishing a design strategy suitable for biomedical applications, we have provided a platform for the engineering of sophisticated, translation-ready DNA nanodevices.

Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system.

Abstract: Nanoparticles represent highly promising platforms for the development of imaging and therapeutic agents, including those that can either be detected via more than one imaging technique (multi-modal imaging agents) or used for both diagnosis and therapy (theranostics). A major obstacle to their medical application and translation to the clinic, however, is the fact that many accumulate in the liver and spleen as a result of opsonization and scavenging by the mononuclear phagocyte system. This focused review summarizes recent efforts to develop zwitterionic-coatings to counter this issue and render nanoparticles more biocompatible. Such coatings have been found to greatly reduce the rate and/or extent of non-specific adsorption of proteins and lipids to the nanoparticle surface, thereby inhibiting production of the "biomolecular corona" that is proposed to be a universal feature of nanoparticles within a biological environment. Additionally, in vivo studies have demonstrated that larger-sized nanoparticles with a zwitterionic coating have extended circulatory lifetimes, while those with hydrodynamic diameters of ≤5 nm exhibit small-molecule-like pharmacokinetics, remaining sufficiently small to pass through the fenestrae and slit pores during glomerular filtration within the kidneys, and enabling efficient excretion via the urine. The larger particles represent ideal candidates for use as blood pool imaging agents, whilst the small ones provide a highly promising platform for the future development of theranostics with reduced side effect profiles and superior dose delivery and image contrast capabilities.

DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination

Abstract: The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored. Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation. These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.

A smart and versatile theranostic nanomedicine platform based on nanoporphyrin

Abstract: Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nanoconstruct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart 'all-in-one' nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumour detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumours. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumours for photothermal therapy (PTT), and light to singlet oxygen for photodynamic therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs or therapeutic radio-metals into tumours.

Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges

Abstract: Introduction: Bearing in mind that many promising drug candidates have the problem of reaching their target site, the concept of advanced drug delivery can play a significant complementary role in shaping modern medicine. Among other nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential in nanomedicine. The intrinsic properties of SPIONs, such as inherent magnetism, broad safety margin and the availability of methods for fabrication and surface engineering, pave the way for diverse biomedical applications. SPIONs can achieve the highest drug targeting efficiency among carriers, since an external magnetic field locally applied to the target organ enhances the accumulation of magnetic nanoparticles in the drug site of action. Moreover, theranostic multifunctional SPIONs make simultaneous delivery and imaging possible. In spite of these favorable qualities, there are some toxicological concerns, such as oxidative stress, unpredictable cellular responses and i...

Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine

Abstract: In the last 30 years we have assisted to a massive advance of nanomaterials in material science. Nanomaterials and structures, in addition to their small size, have properties that differ from those of larger bulk materials, making them ideal for a host of novel applications. The spread of nanotechnology in the last years has been due to the improvement of synthesis and characterization methods on the nanoscale, a field rich in new physical phenomena and synthetic opportunities. In fact, the development of functional nanoparticles has progressed exponentially over the past two decades. This work aims to extensively review 30 years of different strategies of surface modification and functionalization of noble metal (gold) nanoparticles, magnetic nanocrystals and semiconductor nanoparticles, such as quantum dots. The aim of this review is not only to provide in-depth insights into the different biofunctionalization and characterization methods, but also to give an overview of possibilities and limitations of the available nanoparticles.

Gold Nanoparticles: Synthesis and Applications in Drug Delivery

Abstract: This review is focused essentially on the synthesis and applications of gold nanoparticles in the field of medicine and targeted drug delivery. Nanotechnology has become one of the most interesting and advanced areas of research in this field. Among nanoparticles, gold nanoparticles demonstrate special advantages in this field due to their unique properties, small size and high surface area-to-volume ratio. These particles have been widely used in various biomedical applications and drug delivery systems due to their inert nature, stability, high dispersity, non-cytotoxicity and biocompatibility. Keywords : Biosynthesis, Gold nanoparticles, Biomedical applications, Targeted drug delivery, Nanotechnology.

Emerging advances in nanomedicine with engineered gold nanostructures

Abstract: Gold nanostructures possess unique characteristics that enable their use as contrast agents, as therapeutic entities, and as scaffolds to adhere functional molecules, therapeutic cargo, and targeting ligands. Due to their ease of synthesis, straightforward surface functionalization, and non-toxicity, gold nanostructures have emerged as powerful nanoagents for cancer detection and treatment. This comprehensive review summarizes the progress made in nanomedicine with gold nanostructures (1) as probes for various bioimaging techniques including dark-field, one-photon and two-photon fluorescence, photothermal optical coherence tomography, photoacoustic tomography, positron emission tomography, and surface-enhanced Raman scattering based imaging, (2) as therapeutic components for photothermal therapy, gene and drug delivery, and radiofrequency ablation, and (3) as a theranostic platform to simultaneously achieve both cancer detection and treatment. Distinct from other published reviews, this article also discusses the recent advances of gold nanostructures as contrast agents and therapeutic actuators for inflammatory diseases including atherosclerotic plaque and arthritis. For each of the topics discussed above, the fundamental principles and progress made in the past five years are discussed. The review concludes with a detailed future outlook discussing the challenges in using gold nanostructures, cellular trafficking, and translational considerations that are imperative for rapid clinical viability of plasmonic nanostructures, as well as the significance of emerging technologies such as Fano resonant gold nanostructures in nanomedicine.

Nanoparticles for multimodal in vivo imaging in nanomedicine

Abstract: While nanoparticles are usually designed for targeted drug delivery, they can also simultaneously provide diagnostic information by a variety of in vivo imaging methods. These diagnostic capabilities make use of specific properties of nanoparticle core materials. Near-infrared fluorescent probes provide optical detection of cells targeted by real-time nanoparticle-distribution studies within the organ compartments of live, anesthetized animals. By combining different imaging modalities, we can start with deep-body imaging by magnetic resonance imaging or computed tomography, and by using optical imaging, get down to the resolution required for real-time fluorescence-guided surgery.

Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine

Abstract: The ability to find synergic solutions is the core of scientific research and scientific advancement. This is particularly true for medicine, where multimodal imaging and theranostic tools represent the frontier research. Nanotechnology, which by its very nature is multidisciplinary, has opened up the way to the engineering of new organized materials endowed with improved performances. In particular, merging nanoparticles and luminescent signalling can lead to the creation of unique tools for the design of inexpensive, hand-held diagnostic and theranostic kits. In this wide scenario, dye-doped silica nanoparticles constitute very effective nanoplatforms to obtain efficient luminescent, stable, biocompatible and targeted agents for biomedical applications. In this review we discuss the state of the art in the field of luminescent silica-based nanoparticles for medical imaging, starting with an overview of the most common synthetic approaches to these materials. Trying to rationalize the presentation of this extremely multifaceted and complex subject, we have gathered significant examples of systems applied in cancer research, also discussing those that take a multifunctional approach, including theranostic structures. Nanoprobes designed for applications that do not include cancer are a minor part, but interesting achievements have been published and we present a selection of these in the subsequent section. To conclude, we propose a debate on the advantages of creating chemosensors based on luminescent silica nanoparticles. This is far from easy but is a particularly valuable goal in the medical field and therefore subject to extensive research worldwide.

Nanomedicine Scale-up Technologies: Feasibilities and Challenges

Abstract: Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage. The bioactive agent can be combined with a diagnostic agent in a nanodevice for theragnostic applications. However, the formulation scientist faces numerous challenges related to their development, scale-up feasibilities, regulatory aspects, and commercialization. This article reviews recent progress in the method of development of nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up techniques, and challenges in their commercialization.

Nanomedicine and drug delivery: a mini review

Abstract: The field of nanotechnology now has pivotal roles in electronics, biology and medicine. Its application can be appraised, as it involves the materials to be designed at atomic and molecular level. Due to the advantage of their size, nanospheres have been shown to be robust drug delivery systems and may be useful for encapsulating drugs and enabling more precise targeting with a controlled release. In this review specifically, we highlight the recent advances of this technology for medicine and drug delivery systems.

Nanomedicine for drug targeting: strategies beyond the enhanced permeability and retention effect.

Abstract: The growing research interest in nanomedicine for the treatment of cancer and inflammatory-related pathologies is yielding encouraging results. Unfortunately, enthusiasm is tempered by the limited specificity of the enhanced permeability and retention effect. Factors such as lack of cellular specificity, low vascular density, and early release of active agents prior to reaching their target contribute to the limitations of the enhanced permeability and retention effect. However, improved nanomedicine designs are creating opportunities to overcome these problems. In this review, we present examples of the advances made in this field and endeavor to highlight the potential of these emerging technologies to improve targeting of nanomedicine to specific pathological cells and tissues.

Tumor Vasculature Targeted Photodynamic Therapy for Enhanced Delivery of Nanoparticles

Abstract: Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors’ origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as “smart” carriers that site-specifically deliver 1O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine.

Engineering plasmonic metal colloids through composition and structural design.

Abstract: The optical properties of metal nanomaterials are determined by a set of parameters that include composition, particle size and shape, overall architecture, and local environment. This Tutorial Review examines the influence of each of these factors on the localized surface plasmon resonance of colloidal metal nanoparticles. This examination is paralleled with a discussion of the advances which have enabled the synthesis of structurally defined metal nanomaterials, as these samples serve as the best platforms for elucidating the fundamental properties of plasmonic colloids. Based on the analysis of such samples, five guidelines are presented to aid the rational design and synthesis of new metal nanostructures for advanced applications in nanomedicine, energy, chemical sensing, and colloidal plasmonics in general.

Smart chemistry in polymeric nanomedicine

Abstract: This review provides an overview of smart chemistry developed and utilized in the last 5–10 years in polymer-based drug delivery nanomedicine. Smart chemistry not only facilitates the controlled drug loading in a highly specific manner, but also potentially controls the drug release kinetics at the targeted tissues. This review highlights the emergence of new chemistry or unique utilization of conventional chemistry in drug delivery, which is believed to play an important role in developing next generation nanomedicine.

Graphene devices for life

Abstract: Kostas Kostarelos and Kostya S. Novoselov examine the potential of graphene in biomedical applications.

Green Synthesis of Anisotropic Gold Nanoparticles for Photothermal Therapy of Cancer

Abstract: Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800–1000 nm. The particles also showed good biocompatibilit...

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review.

Abstract: Oral cancer (oral cavity and oropharynx) is a common and aggressive cancer that invades local tissue, can cause metastasis, and has a high mortality rate. Conventional treatment strategies, such as surgery and chemoradiotherapy, have improved over the past few decades; however, they remain far from optimal. Currently, cancer research is focused on improving cancer diagnosis and treatment methods (oral cavity and oropharynx) nanotechnology, which involves the design, characterization, production, and application of nanoscale drug delivery systems. In medicine, nanotechnologies, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, cyclodextrin complexes, and liquid crystals, are promising tools for diagnostic probes and therapeutic devices. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for oral cancers.

Drug delivery nanoparticles in skin cancers

Abstract: Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported.