Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

The development of novel therapeutic strategies and modalities for tumors is still one of the important areas of current scientific research. Low permeability and short residence time of drugs in solid tumor areas are important reasons for the low efficiency of existing therapeutic strategies. Typically, nanoparticles with large size displayed enhanced residence time but low permeability. Therefore, to prolong the retention time of materials in solid tumors, size-increasing strategies have been developed to directly generate large-scale nanoparticles using small molecular compounds or increase the size of small nanoparticles in solid tumor areas. In this review, we summarize recently reported activatable aggregation systems that could be activated by cancer-related substances for cancer therapy and classify them by the mechanisms that lead to aggregation. In the end, we propose some potential challenges briefly from the view of our opinion. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Synthetic vectors for therapeutic nucleic acid delivery are currently competing significantly with their viral counter parts due to their reduced immunogenicity, large payload capacity, and ease of manufacture under GMP-compliant norms. The approval of Onpattro, a lipid-based siRNA therapeutic, and the proven clinical success of two lipid-based COVID-19 vaccines from Pfizer-BioNTech, and Moderna heralded the specific advantages of lipid-based systems among all other synthetic nucleic acid carriers. Lipid-based systems with diverse payloads-plasmid DNA (pDNA), antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA), small activating RNA (saRNA), and messenger RNA (mRNA)-are now becoming a mature technology, with growing impact in the clinic. Research over four decades identified the key factors determining the therapeutic success of these multi-component systems. Here, we discuss the main nucleic acid-based technologies, presenting their mechanism of action, delivery barriers facing them, the structural properties of the payload as well as the component lipids that regulate physicochemical properties, pharmacokinetics and biodistribution, efficacy, and toxicity of the resultant nanoparticles. We further detail on the formulation parameters, evolution of the manufacturing techniques that generate reproducible and scalable outputs, and key manufacturing aspects that enable control over physicochemical properties of the resultant particles. Preclinical applications of some of these formulations that were successfully translated from in vitro studies to animal models are subsequently discussed. Finally, clinical success and failure of these systems starting from 1993 to present are highlighted, in a holistic literature review focused on lipid-based nucleic acid delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Chemotherapeutic treatment with conventional drug formulations pose numerous challenges, such as poor solubility, high cytotoxicity and serious off-target side effects, low bioavailability, and ultimately subtherapeutic tumoral concentration leading to poor therapeutic outcomes. In the field of Nanomedicine, advances in nanotechnology have been applied with great success to design and develop novel nanoparticle-based formulations for the treatment of various types of cancer. The approval of the first nanomedicine, Doxil® (liposomal doxorubicin) in 1995, paved the path for further development for various types of novel delivery platforms. Several different types of nanoparticles, especially organic (soft) nanoparticles (liposomes, polymeric micelles, and albumin-bound nanoparticles), have been developed and approved for several anticancer drugs. Nanoparticulate drug delivery platform have facilitated to overcome of these challenges and offered key advantages of improved bioavailability, higher intra-tumoral concentration of the drug, reduced toxicity, and improved efficacy. This review introduces various commonly used nanoparticulate systems in biomedical research and their pharmacokinetic (PK) attributes, then focuses on the various physicochemical and physiological factors affecting the in vivo disposition of chemotherapeutic agents encapsulated in nanoparticles in recent years. Further, it provides a review of the current landscape of soft nanoparticulate formulations for the two most widely investigated anticancer drugs, paclitaxel, and doxorubicin, that are either approved or under investigation. Formulation details, PK profiles, and therapeutic outcomes of these novel strategies have been discussed individually and in comparison, to traditional formulations. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These biomarkers help enrich patients for ICI but are not 100% predictive. Understanding the complex interactions of these biomarkers with other pathways and factors that lead to ICI resistance remains a major goal. Principles of oncophysics-the idea that cancer can be described as a multiscale physical aberration-have shown promise in recent years in terms of capturing the essence of the complexities of ICI interactions. Here, we review the biological knowledge of mechanisms of ICI action and how these are incorporated into modern oncophysics-based mathematical models. Building on the success of oncophysics-based mathematical models may help to discover new, rational methods to engineer immunotherapy for patients in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Early diagnosis of cancer is important to improve the survival rate and relieve patient pain. Sensitive detection of cancer related biomarkers in body fluids is a critical approach for the early diagnosis of cancer. The clustered regularly interspaced short palindromic repeat-associated protein (CRISPR-Cas) system has emerged as a molecular manipulation technology because of its simple detection procedure, high base resolution, and isothermal signal amplification. Recently, various nanomaterials with unique optical and electrical characteristics have been introduced as the novel signal transducers to enhance the detection performance of CRISPR-Cas-based nanosensors. This review summarizes the working mechanisms of the CRISPR-Cas system for biosensing. It also enumerates the strategies of CRISPR-manipulated nanosensors based on various signal models for cancer diagnosis, including colorimetric, fluorescence, electrochemical, electrochemiluminescence, pressure, and other signals. Finally, the prospects and challenges of CRISPR-Cas-based nanosensors for cancer diagnostic are also discussed. This article is categorized under: Diagnostic Tools > Biosensing.

With the continuous development of organic materials for optoelectronic devices and biological applications, J-aggregation has attracted a great deal of interest in both dye chemistry and supramolecular chemistry. Except for the characteristic red-shifted absorption and emission, such ordered head-to-tail stacked structures may be accompanied by special properties such as enhanced absorption, narrowed spectral bandwidth, improved photothermal and photodynamic properties, aggregation-induced emission enhancement (AIEE) phenomenon, and so forth. These excellent properties add great potential to J-aggregates for optical imaging and phototherapy in the near-infrared (NIR) region. Despite decades of development, the challenge of rationally designing the molecular structure to adjust intermolecular forces to induce J-aggregation of organic dyes remains significant. In this review, we discuss the formation of J-aggregates in terms of intermolecular interactions and summarize some recent studies on J-aggregation dyes for NIR imaging and phototherapy, to provide a clear direction and reference for designing J-aggregates of near-infrared organic dyes to better enable biological applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Attempts have been made continuously to use nano-drug delivery system (NDDS) to improve the effect of antitumor therapy. In recent years, especially in the application of immunotherapy represented by antiprogrammed death receptor 1 (anti-PD-1), it has been vigorously developed. Nanodelivery systems are significantly superior in a number of aspects including increasing the solubility of insoluble drugs, enhancing their targeting ability, prolonging their half-life, and reducing side effects. It can not only directly improve the efficacy of anti-PD-1 immunotherapy, but also indirectly enhance the antineoplastic efficacy of immunotherapy by boosting the effectiveness of therapeutic modalities such as chemotherapy, radiotherapy, photothermal, and photodynamic therapy (PTT/PDT). Here, we summarize the studies published in recent years on the use of nanotechnology in pharmaceutics to improve the efficacy of anti-PD-1 antibodies, analyze their characteristics and shortcomings, and combine with the current clinical research on anti-PD-1 antibodies to provide a reference for the design of future nanocarriers, so as to further expand the clinical application prospects of NDDSs. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Single dose slow-release vaccines herald a new era in vaccine administration. An ideal device for slow-release vaccine delivery would be minimally invasive and self-administered, making these approaches an attractive alternative for mass vaccination programs, particularly during the time of a pandemic. In this review article, we discuss the latest advances in this field, specifically for prophylactic vaccines able to prevent infectious diseases. Recent studies have found that slow-release vaccines elicit better immune responses and often do not require cold chain transportation and storage, thus drastically reducing the cost, streamlining distribution, and improving efficacy. This promise has attracted significant attention, especially when poor patient compliance of the standard multidose vaccine regimes is considered. Single dose slow-release vaccines are the next generation of vaccine tools that could overcome most of the shortcomings of present vaccination programs and be the next platform technology to combat future pandemics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Glioblastoma multiforme (GBM) represents the most common and fatal form of primary invasive brain tumors as it affects a great number of patients each year and has a median overall survival of approximately 14.6 months after diagnosis. Despite intensive treatment, almost all patients with GBM experience recurrence, and their 5-year survival rate is approximately 5%. At present, the main clinical treatment strategy includes surgical resection, radiotherapy, and chemotherapy. However, tumor heterogeneity, blood-brain barrier, glioma stem cells, and DNA damage repair mechanisms hinder efficient GBM treatment. The emergence of nanometer-scale diagnostic and therapeutic approaches in cancer medicine due to the establishment of nanotechnology provides novel and promising tools that will allow us to overcome these difficulties. This review summarizes the application and recent progress in nanotechnology-based monotherapies (e.g., chemotherapy) and combination cancer treatment strategies (chemotherapy-based combined cancer therapy) for GBM and describes the synergistic enhancement between these combination therapies as well as the current standard therapy for brain cancer and its deficiencies. These combination therapies that can reduce individual drug-related toxicities and significantly enhance therapeutic efficiency have recently undergone rapid development. The mechanisms underlying these different nanotechnology-based therapies as well as the application of nanotechnology in GBM (e.g., in photodynamic therapy and chemodynamic therapy) have been systematically summarized here in an attempt to review recent developments and to identify promising directions for future research. This review provides novel and clinically significant insights and directions for the treatment of GBM, which is of great clinical importance. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Neural tissue is an electrical responsible organ. The electricity plays a vital role in the growth and development of nerve tissue, as well as the repairing after diseases. The interface between the nervous system and external device for information transmission is called neural electroactive interface. With the development of new materials and fabrication technologies, more and more new types of neural interfaces are developed and the interfaces can play crucial roles in treating many debilitating diseases such as paralysis, blindness, deafness, epilepsy, and Parkinson's disease. Neural interfaces are developing toward flexibility, miniaturization, biocompatibility, and multifunctionality. This review presents the development of neural electrodes in terms of different materials for constructing electroactive neural interfaces, especially focus on the piezoelectric materials-based indirect neuromodulation due to their features of wireless control, excellent effect, and good biocompatibility. We discussed the challenges we need to consider before the application of these new interfaces in clinical practice. The perspectives about future directions for developing more practical electroactive interface in neural engineering are also discussed in this review. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.