Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

While gene therapy has been at the center of an active research field for decades, messenger RNA (mRNA) has long been considered unsuited for therapeutic application due to challenges with stability, immunogenicity, and delivery. Where gene therapy focuses on providing the desired genetic code, mRNA can directly provide the instructions encoded in the corresponding gene. This review aims to explore recent advances in mRNA therapies, building on the success of mRNA COVID-19 vaccines, and extend these insights to the potential treatment of rare genetic diseases. We follow the "outside-in" trajectory of mRNA therapies from administration to intracellular function, focusing on carrier systems such as lipid nanoparticles and virus-like particles, mRNA modifications, and the potential and challenges for clinical applications. To treat rare diseases, different approaches can be envisioned, including chronic or acute delivery of mRNAs encoding functional enzymes for enzyme deficiencies and delivery of CRISPR/Cas9-based gene-editing tools for gene correction. These different approaches determine safety and immunological considerations. By exploring genetic, technical, and therapeutic aspects, this review highlights the potential and current challenges of mRNA therapies to address the large unmet needs in rare genetic disorders.

The field of targeted therapy exploits the selective expression of therapeutic genes or proteins in diseased cells. While this area is gaining attraction in the context of cardiovascular diseases, diabetes, and other major health disorders, it has been most extensively explored in the realm of cancer. Targeted therapy has gained significance in the cancer field for its potential to address the limitations of conventional treatments and enhance patient survival. Interleukin-24 (IL-24), a versatile cytokine, has been evaluated as a cancer therapeutic in various preclinical cancer models and clinical trials, and has yielded promising results. Consequently, multiple studies highlight IL-24 as a viable "anti-cancer" therapeutic, with successful outcomes observed in combination therapies involving small molecule inhibitors, chemotherapeutic drugs, and radiation. Despite the evidence validating the tumor-suppressing properties of IL-24 in cancer models, there is a dearth of information regarding its role in other human diseases. The objective of this review is to offer a synopsis of the potential role of IL-24 in diverse human diseases. Additionally, it provides a comprehensive review of the progress in cancer therapy utilizing IL-24. Finally, from the author's standpoint, the review also addresses some of the limitations that impede the translational potential of IL-24-based therapy in clinical settings. It offers arguments in favor of incorporating IL-24-based targeted therapy as an effective and safer alternative for current treatment modalities, thereby highlighting its potential to revolutionize the field of therapeutics.

Micro/nanorobots are being increasingly utilized as new diagnostic and therapeutic platforms in the biomedical field, enabling remote navigation to hard-to-reach tissues and the execution of various medical procedures. Although significant progress has been made in the development of biomedical micro/nanorobots, how to achieve closed-loop control of them from sensing, memory, and precise trajectory planning to feedback to carry out biomedical tasks remains a challenge. Bacteria with self-propulsion and autonomous intelligence properties are well suited to be engineered as microrobots to achieve closed-loop control for biomedical applications. By virtue of synthetic biology, bacterial microrobots possess an expanded genetic toolbox, allowing them to load input sensors to respond or remember external signals. To achieve accurate control in the complex physiological environment, the development of bacterial microrobots should be matched with the corresponding control system design. In this review, a detailed summary of the sensing and control mechanisms of bacterial microrobots is presented. The engineering and applications of bacterial microrobots in the biomedical field are highlighted. Their future directions of bacterial autonomous intelligent microrobots for precision medicine are forecasted.

The field of nanomedicine offers revolutionary potential to reshape the discovery and development of therapeutics for diverse human diseases. However, its application has been limited in improving Substance Use Disorders (SUDs), which represent a profound public health crisis, including major types such as opioid, alcohol, stimulant, and cannabis use disorders. Pharmacotherapy, a cornerstone of SUD management, has reduced morbidity, mortality, and the societal impact of addiction, though its efficacy has ranged from none to moderate. Thus, there is a major unmet need to transform SUD pharmacotherapy to curb the epidemic of addiction. This article explores the potential roles of nanomedicine-inspired precision-targeted drug delivery, sustained release, and combination therapies to increase therapeutic efficacy and minimize side effects. Additionally, it discusses innovative mechanisms that align with the neurobiological complexities of addiction and synergistic approaches that integrate nanomedicine with behavioral interventions, device-based therapies, and emerging modalities such as immunotherapy and neurostimulation. Despite these advancements, barriers such as treatment accessibility, adherence challenges, and inequitable resource distribution persist, particularly in underserved populations. By harnessing the transformative capabilities of nanomedicine and integrating it into holistic, equitable, and personalized care frameworks, this review highlights a path forward to revolutionize the SUD pharmacotherapy landscape. The article underscores the need for continued nano-SUD pharmacotherapy research and the development of strategies to alleviate the substantial burden of addiction on individuals, families, and society.

Hydrophilic active ingredients play a crucial role in formulated consumer products, encompassing antioxidants, flavoring substances, and pharmaceuticals. Yet, their susceptibility to environmental factors, such as light, pH, temperature, and humidity, poses challenges to their stability and sustained release. Microencapsulation offers a promising avenue to address these challenges, facilitating stabilization, targeted delivery, and enhanced efficacy of hydrophilic actives. However, despite significant advancements in the field, microencapsulation of hydrophilic actives remains at the forefront of innovation. This is primarily due to the intrinsic characteristics of hydrophilic actives, including small molecular weight and thus high permeability through many microcarriers (e.g., shells), which often necessitate complex and costly technologies to be developed. Moreover, in light of escalating regulatory frameworks, the pursuit of biodegradable and other compliant materials suitable for the entrapment of hydrophilic ingredients is gaining momentum. These advancements aim to provide alternatives to currently used non-degradable synthetic polymer materials. Research is currently pushing towards meeting these regulatory constraints via cutting-edge technologies to engineer novel microscale delivery systems for hydrophilic active ingredients, including microcapsules, microspheres, microneedles, and micropatches. Although still in its infancy, this approach holds true potential for revolutionizing the future of formulated consumer goods.

Nucleic acid (NA) therapy holds tremendous potential for treating a wide range of genetic diseases by the delivery of therapeutic genes into target cells. However, significant challenges exist in safely and effectively delivering these genes to their intended locations. Viral vectors, though efficient, pose risks such as immunogenicity and mutagenesis. This has resulted in growing interest in non-viral, nanoparticle-based NA delivery systems. This review article describes various physiological barriers to NA delivery and explores nanoparticle-based NA delivery systems, including bioengineered nanoparticles, peptides, lipid nanoparticles, and polymeric nanoparticles, highlighting their unique features to overcome in vivo barriers for NA delivery. While these nanoparticle-based NA delivery systems offer a promising alternative to viral vectors, challenges related to cytotoxicity, reproducible synthesis, and cost need to be addressed. The current clinical landscape of NA delivery is also discussed, emphasizing the need for safer, scalable, and cost-effective solutions. Nanoparticles represent a promising future in NA therapy, with the possibility of developing clinically relevant, non-toxic, stable, and non-immunogenic delivery vehicles, paving the way for broader therapeutic applications and improved clinical outcomes.

Over the last decades, messenger RNA (mRNA) has emerged as a promising therapeutic modality, enabling the delivery of genetic instructions to cells for producing therapeutic proteins or antigens. As such, mRNA-based therapies can be developed for a wide range of conditions, including infections, cancer, metabolic disorders, and genetic diseases. Nevertheless, using mRNA therapeutically requires chemical modifications to reduce immunostimulatory effects and nanotechnology to prevent degradation and ensure intracellular delivery. Lipid nanoparticles (LNPs) have become the most effective delivery platform for mRNA therapeutics, which are primarily employed for vaccine purposes following local administration and hepatic applications following systemic administration. Here, we review the state-of-the-art LNP-mRNA technology and discuss its potential for immunotherapy. We first outline the requirements for mRNA to be used therapeutically, including the role of LNP-mediated delivery. Next, we highlight LNP-mRNA immunotherapy approaches for vaccination, immuno-oncology, and autoimmune disorders. In addition, we discuss challenges that are limiting LNP-mRNA's widespread use, including tunable biodistribution and immunostimulatory effects. Finally, we provide an outlook on how implementing approaches such as library screening and machine learning will guide the development of next-generation mRNA therapeutics.

Nucleic acid-based vaccines are leading-edge tools in developing next-generation preventative care. Much research has been done to convert vaccine gene therapy from an invasive to a noninvasive administration approach. The lung's large surface area and permeability make the pulmonary route a promising noninvasive delivery option for vaccines, with systemic and local applications. This review summarizes the challenges and the approaches that have been carried out to optimize the delivery of nucleic acids through the pulmonary route for vaccination purposes in recent years, with a spotlight on gold nanoparticles (AuNPs). Nonviral delivery systems have been widely explored, and AuNPs with their unique properties are emerging as promising tools for nucleic acid vaccines due to surface functionalization with mucus-penetrating polymers and targeting moieties that can bypass the barriers in pulmonary delivery and successfully deliver nucleic acids to the cells of interest. However, while promising, several challenges remain including selectively overcoming the lungs' immunological surveillance and adhesive mucus.

Wearable sweat sensors for detecting biochemical markers have emerged as a transformative research area, with the potential to revolutionize disease diagnosis and human health monitoring. Since 2016, a substantial body of pioneering and translational work on sweat biochemical sensors has been reported. This review aims to provide a comprehensive summary of the current state-of-the-art in the field, offering insights and perspectives on future developments. The focus is on wearable microfluidic platforms for sweat collection and delivery and the analytical chemistry applicable to wearable devices. Various microfluidic technologies, including those based on synthetic polymers, paper, textiles, and hydrogels, are discussed alongside diverse detection methods such as electrochemistry and colorimetry. Both the advantages and current limitations of these technologies are critically examined. The review concludes with our perspectives on the future of wearable sweat sensors, with the goal of inspiring new ideas, innovations, and technical advancements to further the development and practical application of these devices in promoting human health.

Cancer remains the leading cause of patient death worldwide and its incidence continues to rise. Immunotherapy is rapidly developing due to its significant differences in the mechanism of action from conventional radiotherapy and targeted antitumor drugs. In the past decades, many biomaterials have been designed and prepared to construct therapeutic platforms that modulate the immune system against cancer. Immunotherapeutic platforms utilizing biomaterials can markedly enhance therapeutic efficacy by optimizing the delivery of therapeutic agents, minimizing drug loss during circulation, and amplifying immunomodulatory effects. The intricate physiological barriers of tumors, coupled with adverse immune environments such as inadequate infiltration, off-target effects, and immunosuppression, have emerged as significant obstacles impeding the effectiveness of oncology drug therapy. However, most of the current studies are devoted to the development of complex immunomodulators that exert immunomodulatory functions by loading drugs or adjuvants, ignoring the complex physiological barriers and adverse immune environments of tumors. Compared with conventional biomaterials, biomimetic nanomaterials based on peptide in situ self-assembly with excellent functional characteristics of biocompatibility, biodegradability, and bioactivity have emerged as a novel and effective tool for cancer immunotherapy. This article presents a comprehensive review of the latest research findings on biomimetic nanomaterials based on peptide in situ self-assembly in tumor immunotherapy. Initially, we categorize the structural types of biomimetic peptide nanomaterials and elucidate their intrinsic driving forces. Subsequently, we delve into the in situ self-assembly strategies of these peptide biomimetic nanomaterials, highlighting their advantages in immunotherapy. Furthermore, we detail the applications of these biomimetic nanomaterials in antigen presentation and modulation of the immune microenvironment. In conclusion, we encapsulate the challenges and prospective developments of biomimetic nanomaterials based on peptide in situ self-assembly for clinical translation in immunotherapy.