Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

mRNA delivery has emerged as a transformative approach in biotechnology and medicine, offering a versatile platform for the development of novel therapeutics. Unlike traditional small molecule drugs or protein-based biologics, mRNA therapeutics have the unique ability to direct cells to generate therapeutic proteins, allowing for precise modulation of biological processes. The delivery of mRNA into target cells is a critical step in realizing the therapeutic potential of this technology. In this review, our focus is on the latest advancements in designing functional polymers to achieve efficient mRNA delivery. Biodegradable polymers and low molecular weight polymers in addressing the balance in mRNA binding and release are summarized. Benefiting from the excellent performance of lipid nanoparticles in mRNA delivery, polymer/lipid hybrid nanostructures are also included. Finally, the challenges and future prospects in the development of polymer-based mRNA delivery systems are discussed.

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We also discuss future research and translational opportunities for nanoparticle-based CT contrast agents enabled by the advent of PCCT and describe key considerations for their clinical translation.

Iron-based nanomaterials (IBNMs) have been widely applied in biomedicine applications including magnetic resonance imaging, targeted drug delivery, tumor therapy, and so forth, due to their unique magnetism, excellent biocompatibility, and diverse modalities. Further research on its enormous biomedical potential is still ongoing, and its new features are constantly being tapped and demonstrated. Among them, various types of IBNMs have demonstrated significant cancer therapy capabilities by regulating the tumor microenvironment (TME). In this review, a variety of IBNMs including iron oxide-based nanomaterials (IONMs), iron-based complex conjugates (ICCs), and iron-based single iron atom nanomaterials (ISANMs) will be introduced, and their advantages in regulating TME would also be emphasized. Besides, the recent progress of IBNMs for cancer diagnosis and treatment through the strategy of modulating TME will be summarized, including overcoming hypoxia, modulating acidity, decreasing redox species, and immunoregulation. Finally, the challenges and opportunities in this field are briefly discussed. This review is expected to contribute to the future design and development of next-generation TME-modulate IBNMs for cancer treatment.

Intrinsically disordered proteins (IDPs) are proteins that, despite lacking a defined 3D structure, are capable of adopting dynamic conformations. This structural adaptability allows them to play not only essential roles in crucial cellular processes, such as subcellular organization or transcriptional control, but also in coordinating the assembly of macromolecules during different stages of development. Thus, in order to artificially replicate the complex processes of morphogenesis and their dynamics, it is crucial to have materials that recapitulate the structural plasticity of IDPs. In this regard, intrinsically disordered protein polymers (IDPPs) emerge as promising materials for engineering synthetic condensates and creating hierarchically self-assembled materials. IDPPs exhibit remarkable properties for their use in biofabrication, such as functional versatility, tunable sequence order-disorder, and the ability to undergo liquid-liquid phase separation (LLPS). Recent research has focused on harnessing the intrinsic disorder of IDPPs to design complex protein architectures with tailored properties. Taking advantage of their stimuli-responsiveness and degree of disorder, researchers have developed innovative strategies to control the self-assembly of IDPPs, resulting in the creation of hierarchically organized structures and intricate morphologies. In this review, we aim to provide an overview of the latest advances in the design and application of IDPP-based materials, shedding light on the fundamental principles that control their supramolecular assembly, and discussing their application in the biomedical and nanobiotechnological fields.

Contrast-enhanced ultrasound is currently used worldwide with clinical indications in cardiology and radiology, and it continues to evolve and develop through innovative technological advancements. Clinically utilized contrast agents for ultrasound consist of hydrophobic gas microbubbles stabilized with a biocompatible shell. These agents are used commonly in echocardiography, with emerging applications in cancer diagnosis and therapy. Microbubbles are a blood pool agent with diameters between 1 and 10 μm, which precludes their use in other extravascular applications. To expand the potential use of contrast-enhanced ultrasound beyond intravascular applications, sub-micron agents, often called nanobubbles or ultra-fine bubbles, have recently emerged as a promising tool. Combining the principles of ultrasound imaging with the unique properties of nanobubbles (high concentration and small size), recent work has established their imaging potential. Contrast-enhanced ultrasound imaging using these agents continues to gain traction, with new studies establishing novel imaging applications. We highlight the recent achievements in nonlinear nanobubble contrast imaging, including a discussion on nanobubble formulations and their acoustic characteristics. Ultrasound imaging with nanobubbles is still in its early stages, but it has shown great potential in preclinical research and animal studies. We highlight unexplored areas of research where the capabilities of nanobubbles may offer new advantages. As technology advances, this technique may find applications in various areas of medicine, including cancer detection and treatment, cardiovascular imaging, and drug delivery.

Early detection of disease remains a crucial challenge in medicine. Delayed diagnosis often leads to limited treatment options, increased disease progression, and unfortunately, even death in some cases. To address this, the need for rapid, cost-effective, and noninvasive diagnostic tools is paramount. In recent years, electrochemical nanosensor-based point-of-care diagnostic tools have emerged as promising tools for various fields, with significant interest in their biological and chemical applications. These tiny sensors, utilizing nanoparticles and chemical agents, can detect and monitor physical components like disease biomarkers at the nanoscale, offering a unique advantage rarely found in other diagnostic methods. This unprecedented sensitivity has made them highly sought-after tools for biological applications, particularly in disease diagnosis. This review focuses specifically on electrochemical nanosensors and their potential as diagnostic tools in medicine. We will delve into their properties, applications, current advancements, and existing limitations.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that often causes joint pain, swelling, and functional impairments. Drug therapy is the main strategy used to alleviate the symptoms of RA; however, drug therapy may have several adverse effects, such as nausea, vomiting, abdominal pain, diarrhea, gastric ulcers, intestinal bleeding, hypertension, hyperglycemia, infection, fatigue, and indigestion. Moreover, long-term excessive use of drugs may cause liver and kidney dysfunction, as well as thrombocytopenia. Nanodrug delivery systems (NDDSs) can deliver therapeutics to diseased sites with the controlled release of the payload in an abnormal microenvironment, which helps to reduce the side effects of the therapeutics. Abnormalities in the microenvironment, such as a decreased pH, increased expression of matrix metalloproteinases (MMPs), and increased concentrations of reactive oxygen species (ROS), are associated with the progression of RA but also provide an opportunity to achieve microenvironment-responsive therapeutic release at the RA site. Microenvironment-responsive NDDSs may overcome the abovementioned disadvantages of RA therapy. Herein, we comprehensively review recent progress in the development of microenvironment-responsive NDDSs for RA treatment, including pH-, ROS-, MMP-, and multiresponsive NDDSs. Furthermore, the pathological microenvironment is highlighted in detail.

Targeted protein degradation (TPD) represents an innovative therapeutic strategy that has garnered considerable attention from both academic and industrial sectors due to its promising developmental prospects. Approximately 85% of human proteins are implicated in disease pathogenesis, and the FDA has approved around 400 drugs targeting these disease-related proteins, predominantly enzymes, transcription factors, and non-enzymatic proteins. However, existing therapeutic modalities fail to address certain "high-value" targets, such as c-Myc and Ras. The emergence of proteolysis-targeting chimeras (PROTAC) technology has introduced TPD into a new realm. The capability to target non-druggable sites has expanded the therapeutic horizon of protein-based drugs, although challenges related to bioavailability, safety, and adverse side effects have constrained their clinical progression. Nano-delivery systems and emerging TPD modalities, such as molecular glues, lysosome-targeted chimeras (LYTACs), autophagy system compounds (ATTEC), and antibody PROTAC (AbTACs), have mitigated some of these limitations. This paper reviews the latest advancements in TPD, highlighting their applications and benefits in cancer therapy, and concludes with a forward-looking perspective on the future development of this field.

Messenger ribonucleic acid (mRNA) therapeutics are attracting attention as promising tools in cancer immunotherapy due to their ability to leverage the in vivo expression of all known protein sequences. Even small amounts of mRNA can have a powerful effect on cancer vaccines by promoting the synthesis of tumor-specific antigens (TSA) or tumor-associated antigens (TAA) by antigen-presenting cells (APC). These antigens are then presented to T cells, eliciting strong antitumor immune stimulation. The potential of mRNA can be further enhanced by expressing immunomodulatory agents, such as cytokines, antibodies, and chimeric antigen receptors (CAR), enhancing tumor immunity. Recent research also explores mRNA-encoded tumor death inducers or tumor microenvironment (TME) modulators. Despite its promise, the clinical translation of mRNA-based anticancer strategies faces challenges, including inefficient targeted delivery in vivo, failure of endosomal escape, and inadequate intracellular mRNA release, resulting in poor transfection efficiencies. Inspired by the approval of lipid nanoparticle-loaded mRNA vaccines against coronavirus disease 2019 (COVID-19) and the encouraging outcomes of mRNA-based cancer therapies in trials, innovative nonviral nanotechnology delivery systems have been engineered. These aim to advance mRNA-based cancer immunotherapies from research to clinical application. This review summarizes recent preclinical and clinical progress in lipid and polymeric nanomedicines for delivering mRNA-encoded antitumor therapeutics, including cytokines and antibody-based immunotherapies, cancer vaccines, and CAR therapies. It also addresses advanced delivery systems for direct oncolysis or TME reprogramming and highlights key challenges in translating these therapies to clinical use, exploring future perspectives, including the role of artificial intelligence and machine learning in their development.

Over the past two decades, ferritin has emerged as a promising nanoparticle for drug delivery, catalyzing the development of numerous prototypes capable of encapsulating a wide array of therapeutic agents. These ferritin-based nanoparticles exhibit selectivity for various molecular targets and are distinguished by their potential biocompatibility, unique symmetrical structure, and highly controlled size. The hollow interior of ferritin nanoparticles allows for efficient encapsulation of diverse therapeutic agents, enhancing their delivery and effectiveness. Despite these promising features, the anticipated clinical advancements have yet to be fully realized. As a physiological protein with a central role in both health and disease, ferritin can exert unexpected effects on physiology when employed as a drug delivery system. Many studies have not thoroughly evaluated the pharmacokinetic properties of the ferritin protein shell when administered in vivo, overlooking crucial aspects such as biodistribution, clearance, cellular trafficking, and immune response. Addressing these challenges is crucial for achieving the desired transition from bench to bedside. Biodistribution studies need to account for ferritin's natural accumulation in specific organs (liver, spleen, and kidneys), which may lead to off-target effects. Moreover, the mechanisms of clearance and cellular trafficking must be elucidated to optimize the delivery and reduce potential toxicity of ferritin nanoparticles. Additionally, understanding the immune response elicited by exogenous ferritin is essential to mitigate adverse reactions and enhance therapeutic efficacy. A comprehensive understanding of these physiological constraints, along with innovative solutions, is essential to fully realize the therapeutic potential of ferritin nanoparticles paving the way for their successful clinical translation.