Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

The adoptive transfer of T cells redirected by chimeric antigen receptors (CARs) has made a dramatic breakthrough in defeating hematological malignancies. However, in solid tumor treatment, CAR-T-cell therapy has attained limited therapeutic benefits due to insufficient infiltration and expansion, rapidly diminishing function following adoptive transfer, and severe life-threatening toxicities. To address these challenges, advancements in nanotechnology have utilized innovative approaches to devise stronger CAR-T cells with reduced toxicity and enhanced anti-tumor activity. Equipping CAR-T cells with multifunctional nanoparticles can abrogate immunosuppressive signaling in the tumor area, augment the functions of CAR-T cells, and mitigate their toxicity against normal tissues. Additionally, nanoparticle-mediated CAR-T-cell programming has the potential to optimize manufacturing and lower the cost for the broader implementation of CAR-T-cell therapy. In this review, we introduce the obstacles to be surmounted in CAR-T-cell therapy, highlight the nanotechnology-based strategies that aim to enrich the therapeutic applications of CAR-T-cell therapy, and envision the prospect of nanoparticle-assisted CAR-T-cell therapy.

Messenger RNA (mRNA) technology has rapidly evolved, significantly impacting various therapeutic applications, including vaccines, protein replacement, and gene editing. Lipid nanoparticles (LNPs) have emerged as a pivotal nonviral vector for mRNA delivery, crucial for organ-targeted therapies. Despite their success, most LNP formulations predominantly target the liver, limiting their use in nonliver diseases. This review explores strategies to achieve organ-specific mRNA delivery using LNPs, including the discovery of new lipid structures, modification of targeting ligands, incorporation of additional components, and optimization of LNP formulations. These advancements aim to enhance the precision and efficacy of mRNA therapeutics across a broader range of diseases.

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA's inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Nanozymes are nanomaterials with intrinsic enzyme-like activity with selected advantages over native enzymes such as simple synthesis, controllable activity, high stability, and low cost. These materials have been explored as surrogates to natural enzymes in biosensing, therapeutics, environmental protection, and many other fields. Among different nanozymes classes, metal- and metal oxide-based nanozymes are the most widely studied. In recent years, bi- and tri-metallic nanomaterials have emerged often showing improved nanozyme activity, some of which even possess multifunctional enzyme-like activity. Taking this concept even further, high-entropy nanomaterials, that is, complex multicomponent alloys and ceramics like oxides, may potentially enhance activity even further. However, the addition of various elements to increase catalytic activity may come at the cost of increased toxicity. Since many nanozyme compositions are currently being explored for in vivo biomedical applications, such as cancer therapeutics, toxicity considerations in relation to nanozyme application in biomedicine are of vital importance for translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Diagnostic Tools > Diagnostic Nanodevices.

Due to its chronic nature and complex pathophysiology, inflammatory bowel disease (IBD) poses significant challenges for treatment. The long-term therapies for patients, often diagnosed between the ages of 20 and 40, call for innovative strategies to target inflammation, minimize systemic drug exposure, and improve patients' therapeutic outcomes. Among the plethora of strategies currently pursued, bioinspired and bioderived nano-based formulations have garnered interest for their safety and versatility in the management of IBD. Bioinspired nanomedicine can host and deliver not only small drug molecules but also biotherapeutics, be made gastroresistant and mucoadhesive or mucopenetrating and, for these reasons, are largely investigated for oral administration, while surprisingly less for rectal delivery, recommended first-line treatment approach for several IBD patients. The use of bioderived nanocarriers, mostly extracellular vesicles (EVs), endowed with unique homing abilities, is still in its infancy with respect to the arsenal of nanomedicine under investigation for IBD treatment. An emerging source of EVs suited for oral administration is ingesta, that is, plants or milk, thanks to their remarkable ability to resist the harsh environment of the upper gastrointestinal tract. Inspired by the unparalleled properties of natural biomaterials, sophisticated avenues for enhancing therapeutic efficacy and advancing precision medicine approaches in IBD care are taking shape, although bottlenecks arising either from the complexity of the nanomedicine designed or from the lack of a clear regulatory pathway still hinder a smooth and efficient translation to the clinics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Polymer-drug conjugates and polymer-protein conjugates have been pivotal in the realm of drug delivery systems for over half a century. These polymeric drugs are characterized by the conjugation of therapeutic molecules or functional moieties to polymers, enabling a range of benefits including extended circulation times, targeted delivery, controlled release, and decreased immunogenicity. This review delves into recent advancements and challenges in the clinical translations and preclinical studies of polymer-drug conjugates and polymer-protein conjugates. The design principles and functionalization strategies crucial for the development of these polymeric drugs were explored followed by the review of structural properties and characteristics of various polymer carriers. This review also identifies significant obstacles in the clinical translation of polymer-drug conjugates and provides insights into the directions for their future development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Radiotherapy is an invaluable tool in the treatment of cancer. However, when used as a monotherapy, it fails to provide curative outcomes. Chemotherapy drugs are often included to boost the effects of radiation. Key classes of radiosensitizing drugs include platinum compounds, anthracyclines, antimetabolites, taxanes, topoisomerase inhibitors, alkylating agents, and DNA damage repair inhibitors. Chemoradiotherapy suffers from not only systemic toxicities from chemotherapy drugs but also synergistic radiation toxicity as well. It is critical to deliver radiosensitizing molecules to tumor cells while avoiding adjacent healthy tissues. Currently, nanomedicine provides an avenue for tumor specific delivery of radiosensitizers. Nanoscale delivery vehicles can be synthesized from lipids, polymers, or inorganic materials. Additionally, nanomedicine encompasses stimuli responsive particles including prodrug formulation for tumor specific activation. Clinically, nanomedicine and radiotherapy are intertwined with approved formulation including DOXIL and Abraxane. Though many challenges remain, the ongoing progress evidences a promising future for both nanomedicine and chemoradiotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Metal Organic Frameworks (MOFs) are an evolving category of crystalline microporous materials that have grabbed the research interest for quite some time due to their admirable physio-chemical properties and easy fabrication methods. Their enormous surface area can be a working ground for innumerable molecular adhesions and site for potential sensor matrices. They have been explored in the last decade for incorporation in electrochemical sensor matrices as diagnostic solutions for a plethora of diseases. This review emphasizes on some of the recent advancements in the area of MOF-based electrochemical biosensors with focus on various important diseases and their significance in upgrading the sensor performance. It summarizes MOF-based biosensors for monitoring biomarkers relevant to diabetes, viral and bacterial sepsis infections, neurological disorders, cardiovascular diseases, and cancer in a wide range of real matrices. The discussion has been supplemented with extensive tables elaborating recent trends in the field of MOF-composite probe fabrication strategies with their respective sensing parameters. The article sums up the future scope of these materials in the field of biosensors and enlightens the reader with recent trends for future research scope. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico-chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off-target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine-based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug-integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Nanomedicines have significantly advanced the development of diagnostic and therapeutic strategies for various diseases, while they still encounter numerous challenges. Upon entry into the human body, nanomedicines interact with biomolecules to form a layer of proteins, which is defined as the protein corona that influences the biological properties of nanomedicines. Traditional approaches have primarily focused on designing stealthy nanomedicines to evade biomolecule adsorption; however, due to the intricacies of the biological environment within body, this method cannot completely prevent biomolecule adsorption. As research on the protein corona progresses, manipulating the protein corona to modulate the in vivo behaviors of nanomedicines has become a research focus. In this review, modern strategies focused on influencing the biological efficacy of nanomedicines in vivo by manipulating protein corona, along with their wide-ranging applications across diverse diseases are critically summarized, highlighted and discussed. Finally, future directions for this important yet challenging research area are also briefly discussed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.