No abstract

Precision medicine has put forward the proposition of "precision targeting" for modern drug delivery systems. Inspired by techniques from biology, pharmaceutical sciences, and nanoengineering, numerous targeted drug delivery systems have been developed in recent decades. But the large-scale applications of these systems are limited due to unsatisfactory targeting efficiency, cytotoxicity, easy removability, and instability. As such, the natural endogenous cargo delivery vehicle—extracellular vesicles (EVs)—have sparked significant interest for its unique inherent targeting properties, biocompatibility, transmembrane ability, and circulatory stability. The membranes of EVs are enriched for receptors or ligands that interact with target cells, which endows them with inherent targeting mission. However, most of the natural therapeutic EVs face the fate of being cleared by macrophages, resulting in off-target. Therefore, the specificity of natural EVs delivery systems urgently needs to be further improved. In this review, we comprehensively summarize the inherent homing mechanisms of EVs and the effects of the donor cell source and administration route on targeting specificity. We then go over nanoengineering techniques that modify EVs for improving specific targeting, such as source cell alteration and modification of EVs surface. We also highlight the auxiliary strategies to enhance specificity by changing the external environment, such as magnetic and photothermal. Furthermore, contemporary issues such as the lack of a gold standard for assessing targeting efficiency are discussed. This review will provide new insights into the development of precision medicine delivery systems. Graphical Abstract

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID‐19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS‐CoV‐2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID‐19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever‐mutating SARS‐CoV‐2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS‐CoV‐2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID‐19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous ‘meet change with constancy’ lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a ‘meet changes with constancy’ strategy to combat SARS‐CoV‐2 that spans defence, antagonism, recovery, and acquired immunity. Targets for COVID‐19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs. Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti‐SARS‐CoV‐2, targeted repair of damaged tissue, and improvement of vaccine efficacy.

The emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes. Graphical Abstract

The gold standard for the repair of bone defects arising from trauma, infection, resection, or tumors continues to be autogenous bone grafting. The healing of autogenous bone grafts is affected by the following local factors: immunological tolerance, blood supply and biological mechanical stress, which cannot be discussed independently without considering the specific sites of the receptor and donor bones. With respect to bone structure, bone composition, the pattern of osteogenesis or embryonic development origins, the site-related differences in properties between long bone and maxillofacial bone are of great importance among the bones distributed throughout the body. Here, we report that grafting bone blocks from mesoderm-derived femurs has poorer restorative performance than grafting bone blocks from cranial neural crest-derived mandibles. Furthermore, there are disparities in osteogenic repair when the same femur block is transplanted to repair defects in different locations (mandible or femur). Specifically, the femur with mandible as the recipient bed shows advantages in newly formed bone area, bone mineral density, collagen fiber structure and mineralization degree. Mechanistically, exosomes of bone marrow mesenchymal stem cells (BMSCs) from the mandible recipient bed mediate the positive healing influence on femur grafting blocks via the miR-126a-5p/Hoxa11 axis during autogenous transdevelopmental lineage transplantation.