Nanomedicine: Engineering Nanocomposite Materials for Cancer Therapy (Small 21/2010)

Cancer accounted for 13% of all deaths worldwide in 2005. Although early detection is critical for the successful treatment of many cancers, there are sensitivity limitations associated with current detection methodologies. Furthermore, many traditional anticancer drug treatments exhibit limited efficacy and cause high morbidity. The unique physical properties of nanoscale materials can be utilized to produce novel and effective sensors for cancer diagnosis, agents for tumor imaging, and therapeutics for cancer treatment. Functionalizing inorganic nanoparticles with biocompatible polymers and natural or rationally designed biomolecules offers a route towards engineering responsive and multifunctional composite systems. Although only a few such innovations have reached human clinical trial to date, nanocomposite materials based on functionalized metal and semiconductor nanoparticles promise to transform the way cancer is diagnosed and treated. This review summarizes the current state‐of‐the‐art in the development of inorganic nanocomposites for cancer‐related applications.     

Near‐Infrared‐Light‐Activatable Nanomaterial‐Mediated Phototheranostic Nanomedicines: An Emerging Paradigm for Cancer Treatment

Cancer is one of the most deadly diseases threatening the lives of humans. Although many treatment methods have been developed to tackle cancer, each modality of cancer treatment has its own limitations and drawbacks. The development of minimally invasive treatment modalities for cancers remains a great challenge. Near‐infrared (NIR) light‐activated nanomaterial‐mediated phototherapies, including photothermal and photodynamic therapies, provide an alternative means for spatially and temporally controlled minimally invasive treatments of cancers. Nanomaterials can serve as nanocargoes for the delivery of chemo‐drugs, diagnostic contrast reagents, and organic photosensitizers, and can be used to directly generate heat or reactive oxygen species for the treatment of tumors without the need for organic photosensitizers with NIR‐light irradiation. Here, current progress in NIR‐light‐activated nanomaterial‐mediated photothermal therapy and photodynamic therapy is summarized. Furthermore, the effects of size, shape, and surface functionalities of nanomaterials on intracellular uptake, macrophage clearance, biodistribution, cytotoxicities, and biomedical efficacies are discussed. The use of various types of nanomaterials, such as gold nanoparticles, carbon nanotubes, graphene, and many other inorganic nanostructures, in combination with diagnostic and therapeutic modalities for solid tumors, is briefly reviewed.     

Micro/Nanoparticle‐Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation

The fast development of photoactivation for cancer treatment provides an efficient photo‐therapeutic strategy for cancer treatment, but traditional photodynamic or photothermal therapy suffers from the critical issue of low in vivo penetration depth of tissues. As a non‐invasive therapeutic modality, sonodynamic therapy (SDT) can break the depth barrier of photoactivation because ultrasound has an intrinsically high tissue‐penetration performance. Micro/nanoparticles can efficiently augment the SDT efficiency based on nanobiotechnology. The state‐of‐art of the representative achievements on micro/nanoparticle‐enhanced SDT is summarized, and specific functions of micro/nanoparticles for SDT are discussed, from the different viewpoints of ultrasound medicine, material science and nanobiotechnology. Emphasis is put on the relationship of structure/composition‐SDT performance of micro/nanoparticle‐based sonosensitizers. Three types of micro/nanoparticle‐augmented SDT are discussed, including organic and inorganic sonosensitizers and micro/nanoparticle‐based but sonosensitizer‐free strategies to enhance the SDT outcome. SDT‐based synergistic cancer therapy augmented by micro/nanoparticles and their biosafety are also included. Some urgent critical issues and potential developments of micro/nanoparticle‐augmented SDT for efficient cancer treatment are addressed. It is highly expected that micro/nanoparticle‐augmented SDT will be quickly developed as a new and efficient therapeutic modality which will find practical applications in cancer treatment. At the same time, fundamental disciplines regarding materials science, chemistry, medicine and nanotechnology will be advanced.     

Nano-magnetic particles used in biomedicine: Core and coating materials

Magnetic nanoparticles for medical applications have been developed by many researchers. Separation, immunoassay, drug delivery, magnetic resonance imaging and hyperthermia are enhanced by the use of suitable magnetic nanoparticles and coating materials in the form of ferrofluids. Due to their low biocompatibility and low dispersion in water solutions, nanoparticles that are used for biomedical applications require surface treatment. Various kinds of coating materials including organic materials (polymers), inorganic metals (gold, platinum) or metal oxides (aluminum oxide, cobalt oxide) have been attracted during the last few years. Based on the recent advances and the importance of nanomedicine in human life, this paper attempts to give a brief summary on the different ferrite nano-magnetic particles and coatings used in nanomedicine.     

Nanoparticle approaches against SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure–function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.     

Understanding and Designing the Gold–Bio Interface: Insights from Simulations

Gold nanoparticles (AuNPs) are an integral part of many exciting and novel biomedical applications, sparking the urgent need for a thorough understanding of the physicochemical interactions occurring between these inorganic materials, their functional layers, and the biological species they interact with. Computational approaches are instrumental in providing the necessary molecular insight into the structural and dynamic behavior of the Au‐bio interface with spatial and temporal resolutions not yet achievable in the laboratory, and are able to facilitate a rational approach to AuNP design for specific applications. A perspective of the current successes and challenges associated with the multiscale computational treatment of Au‐bio interfacial systems, from electronic structure calculations to force field methods, is provided to illustrate the links between different approaches and their relationship to experiment and applications.     

Inorganic lanthanide nanophosphors in biotechnology

Recently different types of fluorescent nanoparticles and other nanostructures have been promoted as alternatives for the fluorescent organic dyes that are traditionally used in biotechnology. Quantum dots, dye-doped polymer and silica particles have found many applications in biochemical protocols and are extensively discussed in the literature. Nanostructures based on inorganic phosphors (nanophosphors) are a new emerging class of materials with unique properties that make them very attractive for bio-application. Some results for the successful application of nanophosphors in biochemical applications have been reported. In this review we summarize the types of materials, their properties that are relevant to bio-applications, and the current status of their implementation in biotechnology.     

NaCl Nanoparticles as a Cancer Therapeutic

Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts. Herein, this preconception is challenged. The study shows that NaCl nanoparticles (SCNPs) but not salts are highly toxic to cancer cells. This is because SCNPs enter cells through endocytosis, bypassing cell regulations on ion transport. When dissolved inside cancer cells, SCNPs cause a surge of osmolarity and rapid cell lysis. Interestingly, normal cells are much more resistant to the treatment due to their relatively low sodium levels. Unlike conventional chemotherapeutics, SCNPs cause immunogenic cell death or ICD. In vivo studies show that SCNPs not only kill cancer cells, but also boost an anticancer immunity. The discovery opens up a new perspective on nanoparticle‐based therapeutics.     

CXCR‐4 Targeted,Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection

Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare‐earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target‐specific identification of subtissue cancerous lesions.     

Nanoparticles for Detection and Treatment of Peripheral Arterial Disease

Peripheral arterial disease (PAD) is defined as a slow, progressive disorder of the lower extremity arterial vessels characterized by chronic narrowing that often results in occlusion and is associated with loss of functional capacity. Although the PAD occurrence rate is increasing in the elderly population, outcomes with current treatment strategies are suboptimal. Hence, there is an urgent need to develop new technologies that overcome limitations of traditional modalities for PAD detection and therapy. In this Review, the application of nanotechnology as a tool that bridges the gap in PAD diagnosis and therapy is in focus. Several materials including synthetic, natural, biodegradable, and biocompatible materials are used to develop nanoparticles for PAD diagnostic and/or therapeutic applications. Moreover, various recent research approaches are being explored to diagnose PAD through multimodality imaging with different nanoplatforms. Further efforts include targeted delivery of various therapeutic agents using nanostructures as carriers to treat PAD. Last, but not least, despite being a fairly new field, researchers are exploring the use of nanotheranostics for PAD detection and therapy.     

Custom-Made Piezoelectric Solid Solution Material for Cancer Therapy

Piezoelectric material-mediated sonodynamic therapy (SDT) has received considerable research interest in cancer therapy. However, the simple applications of conventional piezoelectric materials do not realize the full potential of piezoelectric materials in medicine. Therefore, the energy band structure of a piezoelectric material is modulated in this study to meet the actual requirement for cancer treatment. Herein, an elaborate PEGylated piezoelectric solid solution 0.7BiFeO₃-0.3BaTiO₃ nanoparticles (P-BF-BT NPs) is synthesized, and the resultant particles achieve excellent piezoelectric properties and their band structure is tuned via band engineering. The tuned band structure of P-BF-BT NPs is energetically favorable for the synchronous production of superoxide radicals (•O₂⁻) and oxygen (O₂) self-supply via water splitting by the piezoelectric effect. Besides, the P-BF-BT NPs can initiate the Fenton reaction to generate hydroxyl radical (•OH), and thus, chemodynamic therapy (CDT) can be augmented by ultrasound. Detailed in vitro and in vivo research has verified the promising effects of multimodal imaging-guided P-BF-BT NP-mediated synergistic SDT/CDT by the piezo-Fenton process in hypoxic tumor elimination, accompanied by high therapeutic biosafety. The current demonstrates a novel strategy for designing and synthesizing “custom-made” piezoelectric materials for cancer therapy in the future.     

An inexpensive and efficient method for the synthesis of BTO and STO at temperatures lower than 200 °C

During the past decade the reduction in size of functional architectures has been a dominating trend in many fields of science and technology. The search for electronic materials that can be cheaply solution-processed into nanopowders, while simultaneously providing quality device characteristics, represents a major challenge for material scientists. Solvothermal process is used in order to obtain fine nanoparticles of BaTiO₃ and SrTiO₃ at low temperatures by using an inorganic, ionic precursor. Rietveld refinement proves the presence of a mixture of 65% tetragonal and 35% cubic nanoparticles in the barium titanate powder with an average size of 73 nm and 67 nm, respectively. FTIR shows that an acid treatment allows the elimination of carbonate impurities.     

Recent Advances in 2D Inorganic Nanomaterials for SERS Sensing

Surface‐enhanced Raman spectroscopy is a powerful and sensitive analytical tool that has found application in chemical and biomolecule analysis and environmental monitoring. Since its discovery in the early 1970s, a variety of materials ranging from noble metals to nanostructured materials have been employed as surface enhanced Raman scattering (SERS) substrates. In recent years, 2D inorganic materials have found wide use in the development of SERS‐based chemical sensors owing to their unique thickness dependent physico‐chemical properties with enhanced chemical‐based charge‐transfer processes. Here, recent advances in the application of various 2D inorganic nanomaterials, including graphene, boron nitride, semiconducting metal oxides, and transition metal chalcogenides, in chemical detection via SERS are presented. The background of the SERS concept, including its basic theory and sensing mechanism, along with the salient features of different nanomaterials used as substrates in SERS, extending from monometallic nanoparticles to nanometal oxides, is comprehensively discussed. The importance of 2D inorganic nanomaterials in SERS enhancement, along with their application toward chemical detection, is explained in detail with suitable examples and illustrations. In conclusion, some guidelines are presented for the development of this promising field in the future.     

纳米粒子在润滑材料中的应用进展

介绍了纳米润滑粒子的制备方法,探讨了纳米粒子的润滑机理,包括膜作用机理、类滚珠作用机理和表面优化作用机理.着重综述了纳米粒子在润滑材料中的应用,具体包括:纳米无机粒子可作为添加剂在润滑油、聚合物基复合材料中起抗磨、减摩作用;纳米粒子应用于非聚合物基复合涂层,可形成一种根据环境自我调节的活泼纳米复合涂层,此涂层具有广泛的应用前景.     

Detection of Circulating Cancer Cells Using Electrocatalytic Gold Nanoparticles

A rapid cancer cell detection and quantification assay, based on the electrocatalytic properties of gold nanoparticles towards the hydrogen evolution reaction, is described. The selective labeling of cancer cells is performed in suspension, allowing a fast interaction between the gold nanoparticle labels and the target proteins expressed at the cell membrane. The subsequent electrochemical detection is accomplished with small volumes of sample and user‐friendly equipment through a simple electrochemical method that generates a fast electrochemical response used for the quantification of nanoparticle‐labeled cancer cells. The system establishes a selective cell‐detection assay capable of detecting 4 × 10³ cancer cells in suspension that can be extended to several other cells detection scenarios.     

Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer

Surgical intervention combined with intravesical instillation of chemotherapeutics to clear residual cancer cells after operation is the current standard treatment method for bladder cancer. However, the poor bioavailability of active pharmaceutical ingredients for bladder cancer cells on account of the biological barriers of bladder mucosa, together with significant side effects of currently used intravesical medicine, have limited the clinical outcomes of localized adjuvant therapy for bladder cancer. Aiming at improved intravesical instillation therapy of bladder cancer, a fluorinated polyethylenimine (F‐PEI) is employed here for the transmucosal delivery of an active venom peptide, polybia‐mastoparan I (MPI), which shows selective antiproliferative effect against various bladder cancer cell lines. Upon simple mixing, MPI and F‐PET would coassemble to form stable nanoparticles, which show greatly improved cross‐membrane and transmucosal penetration capacities compared with MPI alone or nonfluorinated MPI/PEI nanoparticles. MPI/F‐PEI shows higher in vivo tumor growth inhibition efficacy for local treatment of a subcutaneous tumor model. More excitingly, as further demonstrated in an orthotopic bladder cancer model, MPI/F‐PEI offers remarkably improved therapeutic effects compared to those achieved by free MPI or the first‐line bladder cancer drug mitomycin C. This work presents a new transmucosal delivery carrier particularly promising for intravesical instillation therapy of bladder cancer.     

Enhanced Sensitivity in Nanopore Sensing of Cancer Biomarkers in Human Blood via Click Chemistry

Cancer biomarkers are expected to be indicative of the occurrence of certain cancer diseases before the tumors form and metastasize. However, many biomarkers can only be acquired in extremely low concentrations, which are often beyond the limit of detection (LOD) of current instruments and technologies. A practical strategy for nanopore sensing of cancer biomarkers in raw human blood down to the femtomolar level is developed here. This strategy first converts the detection of cancer biomarkers to the quantification of copper ions by conducting a sandwich assay involving copper oxide nanoparticles. The released Cu²⁺ is then taken to catalyze the “click” reaction which ligates a host–guest modified DNA probe. Finally, this DNA probe is subjected to single‐channel recordings to afford the translocation events that can be used to derive the concentrations of the original biomarkers. Due to the amplification effects of nanoparticle loadings and the “click” reaction, the LOD of this strategy can be as low as the subfemtomolar level. Further, the acid treatment step could effectively eliminate the interferences from plasma proteins in raw human blood and make the strategy highly suitable for the detection of cancer biomarkers in clinical samples.     

典型无机非金属材料增材制造研究与应用现状

增材制造是基于离散堆积思想实现原型或产品零件的快速制造。作为三大材料之一的无机非金属材料在医疗、航天航空、汽车、建筑、工艺品等众多领域都具有无可比拟的巨大应用前景,为了能够快速制造形状任意复杂的器件,无机非金属材料的增材制造成为当下研究的热点。从增材制造技术类型、材料等方面详细阐述国内外无机非金属材料增材制造研究水平与发展状况,对比几种常用的无机非金属材料,重点是针对几种常见的陶瓷材料以及用于砂型铸造材料等成形特点及面临问题进行阐述,阐明了目前无机非金属材料增材制造存在的迫切需要解决的关键性问题,并深入分析了材料处理工艺、3DP/SLS/SLM三维成形工艺、后处理工艺对成形件的质量和性能的影响作用,最后对宝玉石材料的增材制造提出一些展望。     

Human health hazards of persistent inorganic and carbon nanoparticles

Persistent inorganic and carbon nanoparticles are increasingly engineered for applications and may also be present in conventional materials such as carbon black. Furthermore, they may originate from conventional non particulate materials by processes such as wear and tear. Persistent inorganic and carbon nanoparticles can be hazardous to humans. Relatively much research regards the hazards of inhaled nanoparticles. These may give rise to respiratory disease and to negative effects on other organs, including the cardiovascular system. Determinants of risk of inhaled nanoparticles include: number, size, surface characteristics, shape, structure, and the formation of assemblages. These determinants should preferentially be considered in exposure metrics. A major molecular mechanism underlying the inhalation hazard of nanoparticles is the generation of reactive oxygen species, but other mechanisms such as interactions with proteins and DNA may also contribute. Health hazards may also be linked to ingestion of persistent inorganic and carbon nanoparticles, dermal exposure and exposure of the eye. Standards for workplace exposure to persistent inorganic and carbon are currently emerging and there are options for hazard reduction by elimination and substitution of hazardous nanoparticles and by engineering controls.     

Degradability and Clearance of Inorganic Nanoparticles for Biomedical Applications

Inorganic nanoparticles with tunable and diverse properties hold tremendous potential in the field of nanomedicine, while having non‐negligible toxicity concerns in healthy tissues/organs that have resulted in their restricted clinical translation to date. In the past decade, the emergence of biodegradable or clearable inorganic nanoparticles has made it possible to completely solve this long‐standing conundrum. A comprehensive understanding of the design of these inorganic nanoparticles with their metabolic performance in the body is of crucial importance to advance clinical trials and expand their biological applications in disease diagnosis. Here, a diverse variety of biodegradable or clearable inorganic nanoparticles regarding considerations of the size, morphology, surface chemistry, and doping strategy are highlighted. Their pharmacokinetics, pathways of metabolism in the body, and time required for excretion are discussed. Some inorganic materials intrinsically responsive to various conditions in the tumor microenvironment are also introduced. Finally, an overview of the encountered challenges is provided along with an outlook for applying these inorganic nanoparticles toward future clinical translations.