Showing papers in "Wiley Interdisciplinary Reviews-nanomedicine and Nanobiotechnology in 2017"

Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodal cancer treatment.

Abstract: Photothermal therapy (PTT), in which nanoparticles embedded within tumors generate heat in response to exogenously applied laser light, has been well documented as an independent strategy for highly selective cancer treatment. Gold-based nanoparticles are the main mediators of PTT because they offer: (1) biocompatibility, (2) small diameters that enable tumor penetration upon systemic delivery, (3) simple gold-thiol bioconjugation chemistry for the attachment of desired molecules, (4) efficient light-to-heat conversion, and (5) the ability to be tuned to absorb near-infrared light, which penetrates tissue more deeply than other wavelengths of light. In addition to acting as a standalone therapy, gold nanoparticle-mediated PTT has recently been evaluated in combination with other therapies, such as chemotherapy, gene regulation, and immunotherapy, for enhanced anti-tumor effects. When delivered independently, the therapeutic success of molecular agents is hindered by premature degradation, insufficient tumor delivery, and off-target toxicity. PTT can overcome these limitations by enhancing tumor- or cell-specific delivery of these agents or by sensitizing cancer cells to these additional therapies. All together, these benefits can enhance the therapeutic success of both PTT and the secondary treatment while lowering the required doses of the individual agents, leading to fewer off-target effects. Given the benefits of combining gold nanoparticle-mediated PTT with other treatment strategies, many exciting opportunities for multimodal cancer treatment are emerging that will ultimately lead to improved patient outcomes. WIREs Nanomed Nanobiotechnol 2017, 9:e1449. doi: 10.1002/wnan.1449 For further resources related to this article, please visit the WIREs website.

Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials

Abstract: Nanomedicine is a relatively new field that is rapidly evolving. Formulation of drugs on the nanoscale imparts many physical and biological advantages. Such advantages can in turn translate into improved therapeutic efficacy and reduced toxicity. While approximately 50 nanotherapeutics have already entered clinical practice, a greater number of drugs are undergoing clinical investigation for a variety of indications. This review aims to examine all the nanoformulations that are currently undergoing clinical investigation and their outlook for ultimate clinical translation. WIREs Nanomed Nanobiotechnol 2017, 9:e1416. doi: 10.1002/wnan.1416 For further resources related to this article, please visit the WIREs website.

Stimuli-responsive liposomes for drug delivery.

Abstract: The ultimate goal of drug delivery is to increase the bioavailability and reduce the toxic side effects of the active pharmaceutical ingredient (API) by releasing them at a specific site of action. In the case of antitumor therapy, association of the therapeutic agent with a carrier system can minimize damage to healthy, nontarget tissues, while limit systemic release and promoting long circulation to enhance uptake at the cancerous site due to the enhanced permeation and retention effect (EPR). Stimuli-responsive systems have become a promising way to deliver and release payloads in a site-selective manner. Potential carrier systems have been derived from a wide variety of materials, including inorganic nanoparticles, lipids, and polymers that have been imbued with stimuli-sensitive properties to accomplish triggered release based on an environmental cue. The unique features in the tumor microenvironment can serve as an endogenous stimulus (pH, redox potential, or unique enzymatic activity) or the locus of an applied external stimulus (heat or light) to trigger the controlled release of API. In liposomal carrier systems triggered release is generally based on the principle of membrane destabilization from local defects within bilayer membranes to effect release of liposome-entrapped drugs. This review focuses on the literature appearing between November 2008-February 2016 that reports new developments in stimuli-sensitive liposomal drug delivery strategies using pH change, enzyme transformation, redox reactions, and photochemical mechanisms of activation. WIREs Nanomed Nanobiotechnol 2017, 9:e1450. doi: 10.1002/wnan.1450 For further resources related to this article, please visit the WIREs website.

Complex coacervate-based materials for biomedicine.

Abstract: There has been increasing interest in complex coacervates for deriving and transporting biomaterials. Complex coacervates are a dense, polyelectrolyte-rich liquid that results from the electrostatic complexation of oppositely charged macroions. Coacervates have long been used as a strategy for encapsulation, particularly in food and personal care products. More recent efforts have focused on the utility of this class of materials for the encapsulation of small molecules, proteins, RNA, DNA, and other biomaterials for applications ranging from sensing to biomedicine. Furthermore, coacervate-related materials have found utility in other areas of biomedicine, including cartilage mimics, tissue culture scaffolds, and adhesives for wet, biological environments. Here, we discuss the self-assembly of complex coacervate-based materials, current challenges in the intelligent design of these materials, and their utility applications in the broad field of biomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1442. doi: 10.1002/wnan.1442 For further resources related to this article, please visit the WIREs website.

Nanoescapology: progress toward understanding the endosomal escape of polymeric nanoparticles

Abstract: Using nanoparticles to deliver drugs to cells has the potential to revolutionize the treatment of many diseases, including HIV, cancer, and diabetes. One of the major challenges facing this field is controlling where the drug is trafficked once the nanoparticle is taken up into the cell. In particular, if drugs remain localized in an endosomal or lysosomal compartment, the therapeutic can be rendered completely ineffective. To ensure the design of more effective delivery systems we must first develop a better understanding of how nanoparticles and their cargo are trafficked inside cells. This needs to be combined with an understanding of what characteristics are required for nanoparticles to achieve endosomal escape, along with methods to detect endosomal escape effectively. This review is focused into three sections: first, an introduction to the mechanisms governing internalization and trafficking in cells, second, a discussion of methods to detect endosomal escape, and finally, recent advances in controlling endosomal escape from polymer- and lipid-based nanoparticles, with a focus on engineering materials to promote endosomal escape. WIREs Nanomed Nanobiotechnol 2017, 9:e1452. doi: 10.1002/wnan.1452 For further resources related to this article, please visit the WIREs website.

High throughput toxicity screening and intracellular detection of nanomaterials

Abstract: With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety-preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read-across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter-experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM-cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose- and time-dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label-free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance-based monitoring, Multiplex analysis of secreted products, and genotoxicity methods-namely High throughput comet assay, High throughput in vitro micronucleus assay, and γH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413 For further resources related to this article, please visit the WIREs website.

Dendrimer-based nanocarriers: a versatile platform for drug delivery.

Abstract: Advances in nanotechnology have had profound impacts on therapeutic delivery, leading to the development of nanomaterials engineered with large carrying capabilities and targeting functionalities. Among the nanomaterials, dendrimers have garnered particular attention from researchers owing to their well-defined structure, near-monodispersity, and ease of multifunctionalization. As hyperbranched, three-dimensional macromolecules, dendrimers can be engineered to target and deliver a wide range of therapeutic agents, including small molecules, peptides, and genes, reducing their systemic toxicities and enhancing efficacies. In this review, we provide a comprehensive overview of the commonly employed dendrimer-based nanocarrier designs, including dendrimer conjugates, Janus dendrimers, and linear-dendritic block copolymers. The discussion will progress through the basic synthetic strategies of dendrimer-based nanocarriers, followed by the potential clinical applications related to their unique structural properties. Finally, the major challenges that these nanocarriers are currently facing in their clinical translation and possible solutions to address these issues will be discussed, with the aim to provide researchers in the drug delivery field a good understanding of the potential utilities of dendrimer-based nanocarriers. WIREs Nanomed Nanobiotechnol 2017, 9:e1409. doi: 10.1002/wnan.1409 For further resources related to this article, please visit the WIREs website.

Recent applications of phthalocyanines and naphthalocyanines for imaging and therapy.

Abstract: With high extinction coefficients and long absorption wavelengths in the near infrared region, phthalocyanines (Pcs) and naphthalocyanines (Ncs) are well-suited for optical imaging and phototherapies in biological tissues. Pcs and Ncs have been used in a range of theranostic applications. Peripheral and axial substituents can be introduced to Pcs and Ncs for chemical modification. Seamless metal chelation of Pcs or Ncs can expand their possibilities as medical therapeutic and imaging agents. Nanoparticulate approaches enable unique ways to deliver Pcs and Ncs to target tissues and improve their solubility, biocompatibility, biodistribution and stability. Herein, we highlight some recent Pc or Nc nanoscale systems for theranostic applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1420. doi: 10.1002/wnan.1420 For further resources related to this article, please visit the WIREs website.

Protein corona and nanoparticles: how can we investigate on?

Abstract: Nanoparticles (NPs) represent one of the most promising tools for drug-targeting and drug-delivery. However, a deeper understanding of the complex dynamics that happen after their in vivo administration is required. Particularly, plasma proteins tend to associate to NPs, forming a new surface named the 'protein corona' (PC). This surface is the most exposed as the 'visible side' of NPs and therefore, can have a strong impact on NP biodistribution, targeting efficacy and also toxicity. The PC consists of two poorly delimited layers, known as 'hard corona' (HC) and 'soft corona' (SC), that are affected by the complexity of the environment and the formed protein-surface equilibrium during in vivo blood circulation. The HC corona is formed by proteins strongly associated to the NPs, while the SC is an outer layer consisting of loosely bound proteins. Several studies attempted to investigate the HC, which is easier to be isolated, but yielded poor reproducibility, due to varying experimental conditions. As a consequence, full mapping of the HC for different NPs is still lacking. Moreover, the current knowledge on the SC, which may play a major role in the 'first' interaction of NPs once in vivo, is very limited, mainly due to the difficulties in preserving it after purification. Therefore, multi-disciplinary approaches leading to the obtainment of a major number of information about the PC and its properties is strongly needed to fully understand its impact and to better support a more safety and conscious application of nanotechnology in medicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1467. doi: 10.1002/wnan.1467 For further resources related to this article, please visit the WIREs website.

What is new in nanoparticle-based photoacoustic imaging?

Abstract: Photoacoustic imaging combines the high temporal and spatial resolution of ultrasound with the good contrast and spectral tuning of optical imaging. Contrast agents are used in photoacoustic imaging to further increase the contrast and specificity of imaging or to image a specific molecular process, e.g., cell-surface proteins or small molecule biomarkers. Nanoparticle-based contrast agents are important tools in photoacoustic imaging because they offer intense and stable signal and can be targeted to specific molecular processes. In this review, we describe some of the most interesting and recent advances in nanoparticle-based photoacoustic imaging including inorganic nanoparticles, organic/polymeric nanoparticles, nanoparticle coatings, multimodality imaging, as well as emerging topics in the field. WIREs Nanomed Nanobiotechnol 2017, 9:e1404. doi: 10.1002/wnan.1404 For further resources related to this article, please visit the WIREs website.

Recent advances of using polyhydroxyalkanoate-based nanovehicles as therapeutic delivery carriers.

Abstract: Polyhydroxyalkanoates (PHAs) are a class of diverse biodegradable polyesters that can be produced either by natural bioconversion process or by chemical synthesis via the ring-opening polymerization of β-lactones. Because of the excellent biodegradability and biocompatibility, the development of PHA-based nanovehicles as therapeutic delivery carriers, including nanoparticles, micelles, liposomes, and vesicles, has received considerable attention in recent years, and these sophisticated materials have demonstrated significant impact on the drug bioavailability, better encapsulation, and less toxic properties of biodegradable polymers. In this review, the most recent advances of using PHA-based nanovehicles as therapeutic delivery carriers are summarized with respect to different material types including intrinsic bulk PHA and functionalized PHA through biological and chemical approaches. The bio-significance of using different carriers in the controlled and targeted delivery of hydrophobic drugs, proteins, vaccines, nucleic acids (DNA and siRNA), and biological macromolecules in cancer therapy is also discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1429. doi: 10.1002/wnan.1429 For further resources related to this article, please visit the WIREs website.

Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety.

Abstract: Cerium oxide nanoparticles have widespread use in the materials industry, and have recently come into consideration for biomedical use due to their potent regenerative antioxidant properties. Given that the brain is one of the most highly oxidative organs in the body, it is subject to some of the greatest levels of oxidative stress, particularly in neurodegenerative disease. Therefore, cerium oxide nanoparticles are currently being investigated for efficacy in several neurodegenerative disorders and have shown promising levels of neuroprotection. This review discusses the basis for cerium oxide nanoparticle use in neurodegenerative disease and its hypothesized mechanism of action. The review focuses on an up-to-date summary of in vivo work with cerium oxide nanoparticles in animal models of neurodegenerative disease. Additionally, we examine the current state of information regarding biodistribution, toxicity, and safety for cerium oxide nanoparticles at the in vivo level. Finally, we discuss future directions that are necessary if this nanopharmaceutical is to move up from the bench to the bedside. WIREs Nanomed Nanobiotechnol 2017, 9:e1444. doi: 10.1002/wnan.1444 For further resources related to this article, please visit the WIREs website.

Detection and treatment of atherosclerosis using nanoparticles

Abstract: Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, and the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells, and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely, and effectively detect the lesions in the early stages, nor can they characterize the lesion features such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects. WIREs Nanomed Nanobiotechnol 2017, 9:e1412. doi: 10.1002/wnan.1412 For further resources related to this article, please visit the WIREs website.

Delivery of therapeutics with nanoparticles: what's new in cancer immunotherapy?

Abstract: The application of nanotechnology to the treatment of cancer or other diseases has been boosted during the last decades due to the possibility to precise deliver drugs where needed, enabling a decrease in the drug's side effects. Nanocarriers are particularly valuable for potentiating the simultaneous co-delivery of multiple drugs in the same particle for the treatment of heavily burdening diseases like cancer. Immunotherapy represents a new concept in the treatment of cancer and has shown outstanding results in patients treated with check-point inhibitors. Thereby, researchers are applying nanotechnology to cancer immunotherapy toward the development of nanocarriers for delivery of cancer vaccines and chemo-immunotherapies. Cancer nanovaccines can be envisioned as nanocarriers co-delivering antigens and adjuvants, molecules often presenting different physicochemical properties, in cancer therapy. A wide range of nanocarriers (e.g., polymeric, lipid-based and inorganic) allow the co-formulation of these molecules, or the delivery of chemo- and immune-therapeutics in the same system. Finally, there is a trend toward the use of biologically inspired and derived nanocarriers. In this review, we present the recent developments in the field of immunotherapy, describing the different systems proposed by categories: polymeric nanoparticles, lipid-based nanosystems, metallic and inorganic nanosystems and, finally, biologically inspired and derived nanovaccines. WIREs Nanomed Nanobiotechnol 2017, 9:e1421. doi: 10.1002/wnan.1421 For further resources related to this article, please visit the WIREs website.

Recent advances in aliphatic polyesters for drug delivery applications.

Abstract: The use of aliphatic polyesters in drug delivery applications has been a field of significant interest spanning decades. Drug delivery strategies have made abundant use of polyesters in their structures owing to their biocompatibility and biodegradability. The properties afforded from these materials provide many avenues for the tunability of drug delivery systems to suit individual needs of diverse applications. Polyesters can be formed in several different ways, but the most prevalent is the ring-opening polymerization of cyclic esters. When used to form amphiphilic block copolymers, these materials can be utilized to form various drug carriers such as nanoparticles, micelles, and polymersomes. These drug delivery systems can be tailored through the addition of targeting moieties and the addition of stimuli-responsive groups into the polymer chains. There are also different types of polyesters that can be used to modify the degradation rates or mechanical properties. Here, we discuss the reasons that polyesters have become so popular, the current research focuses, and what the future holds for these materials in drug delivery applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1446. doi: 10.1002/wnan.1446 For further resources related to this article, please visit the WIREs website.

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles

Abstract: Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website.

Synthetic plant virology for nanobiotechnology and nanomedicine.

Abstract: Nanotechnology is a rapidly expanding field seeking to utilize nano-scale structures for a wide range of applications. Biologically derived nanostructures, such as viruses and virus-like particles (VLPs), provide excellent platforms for functionalization due to their physical and chemical properties. Plant viruses, and VLPs derived from them, have been used extensively in biotechnology. They have been characterized in detail over several decades and have desirable properties including high yields, robustness, and ease of purification. Through modifications to viral surfaces, either interior or exterior, plant-virus-derived nanoparticles have been shown to support a range of functions of potential interest to medicine and nano-technology. In this review we highlight recent and influential achievements in the use of plant virus particles as vehicles for diverse functions: from delivery of anticancer compounds, to targeted bioimaging, vaccine production to nanowire formation. WIREs Nanomed Nanobiotechnol 2017, 9:e1447. doi: 10.1002/wnan.1447 For further resources related to this article, please visit the WIREs website.

Advances in the development of aptamer drug conjugates for targeted drug delivery.

Abstract: A key goal of modern medicine is target-specific therapeutic intervention However, most drugs lack selectivity, resulting in ‘off-target’ side effects To address the requirements of ‘targeted therapy,’ aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates (ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy WIREs Nanomed Nanobiotechnol 2017, 9:e1438 doi: 101002/wnan1438 For further resources related to this article, please visit the WIREs website

Graphene oxide as a scaffold for bone regeneration

Abstract: Graphene oxide (GO), the oxidized form of graphene, holds great potential as a component of biomedical devices, deriving utility from its ability to support a broad range of chemical functionalities and its exceptional mechanical, electronic, and thermal properties. GO composites can be tuned chemically to be biomimetic, and mechanically to be stiff yet strong. These unique properties make GO-based materials promising candidates as a scaffold for bone regeneration. However, questions still exist as to the compatibility and long-term toxicity of nanocarbon materials. Unlike other nanocarbons, GO is meta-stable, water dispersible, and autodegrades in water on the timescale of months to humic acid-like materials, the degradation products of all organic matter. Thus, GO offers better prospects for biological compatibility over other nanocarbons. Recently, many publications have demonstrated enhanced osteogenic performance of GO-containing composites. Ongoing work toward surface modification or coating strategies could be useful to minimize the inflammatory response and improve compatibility of GO as a component of medical devices. Furthermore, biomimetic modifications could offer mechanical and chemical environments that encourage osteogenesis. So long as care is given to assure their safety, GO-based materials may be poised to become the next generation scaffold for bone regeneration. WIREs Nanomed Nanobiotechnol 2017, 9:e1437. doi: 10.1002/wnan.1437 For further resources related to this article, please visit the WIREs website.

Cryo-electron microscopy and cryo-electron tomography of nanoparticles

Abstract: Cryo-transmission electron microscopy (cryo-TEM or cryo-EM) and cryo-electron tomography (cryo-ET) offer robust and powerful ways to visualize nanoparticles. These techniques involve imaging of the sample in a frozen-hydrated state, allowing visualization of nanoparticles essentially as they exist in solution. Cryo-TEM grid preparation can be performed with the sample in aqueous solvents or in various organic and ionic solvents. Two-dimensional (2D) cryo-TEM provides a direct way to visualize the polydispersity within a nanoparticle preparation. Fourier transforms of cryo-TEM images can confirm the structural periodicity within a sample. While measurement of specimen parameters can be performed with 2D TEM images, determination of a three-dimensional (3D) structure often facilitates more spatially accurate quantization. 3D structures can be determined in one of two ways. If the nanoparticle has a homogeneous structure, then 2D projection images of different particles can be averaged using a computational process referred to as single particle reconstruction. Alternatively, if the nanoparticle has a heterogeneous structure, then a structure can be generated by cryo-ET. This involves collecting a tilt-series of 2D projection images for a defined region of the grid, which can be used to generate a 3D tomogram. Occasionally it is advantageous to calculate both a single particle reconstruction, to reveal the regular portions of a nanoparticle structure, and a cryo-electron tomogram, to reveal the irregular features. A sampling of 2D cryo-TEM images and 3D structures are presented for protein based, DNA based, lipid based, and polymer based nanoparticles. WIREs Nanomed Nanobiotechnol 2017, 9:e1417. doi: 10.1002/wnan.1417 For further resources related to this article, please visit the WIREs website.

Tumor‐targeted nanotherapeutics: overcoming treatment barriers for glioblastoma

Abstract: Glioblastoma (GBM) is a highly aggressive and lethal form of primary brain cancer. Numerous barriers exist to the effective treatment of GBM including the tightly controlled interface between the bloodstream and central nervous system termed the 'neurovascular unit,' a narrow and tortuous tumor extracellular space containing a dense meshwork of proteins and glycosaminoglycans, and genomic heterogeneity and instability. A major goal of GBM therapy is achieving sustained drug delivery to glioma cells while minimizing toxicity to adjacent neurons and glia. Targeted nanotherapeutics have emerged as promising drug delivery systems with the potential to improve pharmacokinetic profiles and therapeutic efficacy. Some of the key cell surface molecules that have been identified as GBM targets include the transferrin receptor, low-density lipoprotein receptor-related protein, αv β3 integrin, glucose transporter(s), glial fibrillary acidic protein, connexin 43, epidermal growth factor receptor (EGFR), EGFR variant III, interleukin-13 receptor α chain variant 2, and fibroblast growth factor-inducible factor 14. However, most targeted therapeutic formulations have yet to demonstrate improved efficacy related to disease progression or survival. Potential limitations to current targeted nanotherapeutics include: (1) adhesive interactions with nontarget structures, (2) low density or prevalence of the target, (3) lack of target specificity, and (4) genetic instability resulting in alterations of either the target itself or its expression level in response to treatment. In this review, we address these potential limitations in the context of the key GBM targets with the goal of advancing the understanding and development of targeted nanotherapeutics for GBM. WIREs Nanomed Nanobiotechnol 2017, 9:e1439. doi: 10.1002/wnan.1439 For further resources related to this article, please visit the WIREs website.

Photoactivated drug delivery and bioimaging

Abstract: Among the various types of diseases, cancer remains one of the most leading causes of mortality that people are always suffering from and fighting with. So far, the effective cancer treatment demands accurate medical diagnosis, precise surgery, expensive medicine administration, which leads to a significant burden on patients, their families, and the whole national healthcare system around the world. In order to increase the therapeutic efficiency and minimize side effects in cancer treatment, various kinds of stimuli-responsive drug delivery systems and bioimaging platforms have been extensively developed within the past decades. Among them, the strategy of photoactivated approach has attracted considerable research interest because light enables the precise control, in a highly spatial and temporal manner, the release of drug molecules as well as the activation of bioimaging agents. In general, several appropriate photoresponsive systems, which are normally sensitive to ultraviolet (UV) or visible light irradiation to undergo the multiple reaction pathways such as photocleavage and photoisomerization strategy etc. have been mainly involved in the light activated cancer therapies. Considering the potential issues of poor tissue penetration and high photoctotoxicity of short wavelength light, the recently emerged therapies based on long-wavelength irradiation, e.g., near-infrared (NIR) light (700-1000 nm), have displayed distinct advantages in biomedical applications. The light irradiation at NIR window indicates minimized photodamage, deep penetration, and low autofluorescence in living cells and tissues, which are of clinical importance in the desired diagnosis and therapy. In this review article, we introduce the recent advances in light-activated drug release and biological imaging mainly for anticancer treatment. Various types of strategies such as photocage, photo-induced isomerization, optical upconversion, and photothermal release by which different wavelength ranges of light can play the important roles in the controlled therapeutic or imaging agents delivery, and activation will be systemically discussed. In addition, the challenges and future perspectives for photo-based cancer theranostics will be also summarized. WIREs Nanomed Nanobiotechnol 2017, 9:e1408. doi: 10.1002/wnan.1408 For further resources related to this article, please visit the WIREs website.

Multifunctional nanoparticle composites: progress in the use of soft and hard nanoparticles for drug delivery and imaging.

Abstract: With continued advancements in nanoparticle (NP) synthesis and in the interfacing of NPs with biological systems has come the exponential growth in the use of NPs for therapeutic drug delivery and imaging applications. In recent years, the advent of NP multifunctionality-the ability to perform multiple, disparate functions on a single NP platform-has garnered much excitement for the potential realization of highly functional NP-mediated drug delivery for use in the clinical setting. This Overview will survey the current state of the art (reports published within the last 5 years) of multifunctional NPs for therapeutic drug delivery, imaging or a combination thereof. We provide extensive examples of both soft (micelles, liposomes, polymeric NPs) and hard (noble metals, quantum dots, metal oxides) NP formulations that have been used for multimodal drug delivery and imaging. The criteria for inclusion, herein, is that there must be at least two therapeutic drug cargos or imaging agents or a combination of the two. We next offer an assessment of the cytotoxicity of therapeutic NP constructs in biological systems. We then conclude with a forward-looking perspective on how we expect this field to develop in the coming years. WIREs Nanomed Nanobiotechnol 2017, 9:e1466. doi: 10.1002/wnan.1466 For further resources related to this article, please visit the WIREs website.

Bio-inspired nanomedicine strategies for artificial blood components.

Abstract: Blood is a fluid connective tissue where living cells are suspended in noncellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune surveillance (WBCs) and hemostatic responses (platelets), and the noncellular components (salts, proteins, etc.) provide nutrition to various tissues in the body. Dysfunction and deficiencies in these blood components can lead to significant tissue morbidity and mortality. Consequently, transfusion of whole blood or its components is a clinical mainstay in the management of trauma, surgery, myelosuppression, and congenital blood disorders. However, donor-derived blood products suffer from issues of shortage in supply, need for type matching, high risks of pathogenic contamination, limited portability and shelf-life, and a variety of side-effects. While robust research is being directed to resolve these issues, a parallel clinical interest has developed toward bioengineering of synthetic blood substitutes that can provide blood's functions while circumventing the above problems. Nanotechnology has provided exciting approaches to achieve this, using materials engineering strategies to create synthetic and semi-synthetic RBC substitutes for enabling oxygen transport, platelet substitutes for enabling hemostasis, and WBC substitutes for enabling cell-specific immune response. Some of these approaches have further extended the application of blood cell-inspired synthetic and semi-synthetic constructs for targeted drug delivery and nanomedicine. The current study provides a comprehensive review of the various nanotechnology approaches to design synthetic blood cells, along with a critical discussion of successes and challenges of the current state-of-art in this field. WIREs Nanomed Nanobiotechnol 2017, 9:e1464. doi: 10.1002/wnan.1464 For further resources related to this article, please visit the WIREs website.

α-Helical coiled-coil peptide materials for biomedical applications.

Abstract: Self-assembling coiled coils, which occur commonly in native proteins, have received significant interest for the design of new biomaterials-based medical therapies. Considerable effort over recent years has led to a detailed understanding of the self-assembly process of coiled coils, and a diverse collection of strategies have been developed for designing functional materials using this motif. The ability to engineer the interface between coiled coils allows one to achieve variously connected components, leading to precisely defined structures such as nanofibers, nanotubes, nanoparticles, networks, gels, and combinations of these. Currently these materials are being developed for a range of biotechnological and medical applications, including drug delivery systems for controlled release, targeted nanomaterials, 'drug-free' therapeutics, vaccine delivery systems, and others. WIREs Nanomed Nanobiotechnol 2017, 9:e1424. doi: 10.1002/wnan.1424 For further resources related to this article, please visit the WIREs website.

Functional carbon nanodots for multiscale imaging and therapy

Abstract: As an emerging class of carbon nanomaterials, carbon dots (CDs) have garnered many researchers' interests in the past decade due to their excellent biocompatibility, replete surface functional groups, water dispersibility, and unique photoluminescence These extraordinary properties have opened new avenues for their advanced application in cell labeling, bioimaging, drug delivery, sensors, and energy-related devices In this paper, we critically review recent advances in the synthetic strategies and the application of CDs for biological purposes, specifically, imaging and therapy Finally, a perspective has been given on the potential challenges facing the translation of these materials from the bench to the market WIREs Nanomed Nanobiotechnol 2017, 9:e1436 doi: 101002/wnan1436 For further resources related to this article, please visit the WIREs website

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

Abstract: Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. WIREs Nanomed Nanobiotechnol 2017, 9:e1403. doi: 10.1002/wnan.1403 For further resources related to this article, please visit the WIREs website.

Nanomedicine approaches to improve cancer immunotherapy

Abstract: Significant advances have been made in the field of cancer immunotherapy by orchestrating the body's immune system to eradicate cancer cells. However, safety and efficacy concerns stemming from the systemic delivery of immunomodulatory compounds limits cancer immunotherapies expansion and application. In this context, nanotechnology presents a number of advantages, such as targeted delivery to immune cells, enhanced clinical outcomes, and reduced adverse events, which may aid in the delivery of cancer vaccines and immunomodulatory agents. With this in mind, a diverse range of nanomaterials with different physicochemical characteristics have been developed to stimulate the immune system and battle cancer. In this review, we will focus on some recent developments and the potential advantages of utilizing nanotechnology within the field of cancer immunotherapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1456. doi: 10.1002/wnan.1456 For further resources related to this article, please visit the WIREs website.

Multifunctional platinum-based nanoparticles for biomedical applications.

Abstract: Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier-based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor-specific localization as well as tumor cell uptake. The introduction of stimuli-responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor-localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real-time monitoring the distribution of drug-loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum-based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 For further resources related to this article, please visit the WIREs website.

Renal clearable noble metal nanoparticles: photoluminescence, elimination, and biomedical applications

Abstract: Metal nanoparticles have demonstrated broad and promising biomedical applications in research laboratories, but how to fulfill their promises in the clinical practices demands extensive effort to minimize their non-specific accumulation in the body. In the past 6 years, we have developed a class of renal clearable noble metal nanoparticles with tunable visible and near-infrared emission, which can behave like small molecular contrast agents to be effectively eliminated through the kidneys. By taking advantage of the unique clearance pathway, we were able to gain some fundamental understanding of how engineering nanoparticles cleared out of the body through urinary system. Moreover, they also provided unique opportunities in early cancer detection and kidney functional imaging that were often challenging to be achieved with non-renal clearable nanoparticles and small molecular probes. In this review, we summarize key factors that govern in the renal clearance of luminescent noble metal nanoparticles and their strengths in cancer targeting and kidney functional imaging. At the end, we also outline several key challenges that need to be addressed before they can be considered in the clinical practices. For further resources related to this article, please visit the WIREs website.