Bioinspired cellular membrane-derived vesicles for mRNA delivery.

The rapid advancement of mRNA as vaccines and therapeutic agents in the biomedical field has sparked hope in the fight against untreatable diseases. Successful clinical application of mRNA therapeutics largely depends on the carriers. Recently, a new and exciting focus has emerged on natural cell-derived vesicles. These nanovesicles offer many functions, including enhanced drug delivery capabilities and immune evasion, thereby presenting a unique and promising platform for the effective and safe delivery of mRNA therapeutics. In this study, we summarize the characteristics and properties of biomimetic delivery systems for mRNA therapeutics. In particular, we discuss the unique features of cellular membrane-derived vesicles (CDVs) and the combination of synthetic nanovesicles with CDVs.

Bone Targeting Nanoparticles for the Treatment of Osteoporosis.

Osteoporosis (OP) affects millions of people worldwide, especially postmenopausal women and the elderly. Although current available anti-OP agents can show promise in slowing down bone resorption, most are not specifically delivered to the hard tissue, causing significant toxicity. A bone-targeted nanodrug delivery system can reduce side effects and precisely deliver drug candidates to the bone. This review focuses on the progress of bone-targeted nanoparticles in OP therapy. We enumerate the existing OP medications, types of bone-targeted nanoparticles and categorize pairs of the most common bone-targeting functional groups. Finally, we summarize the potential use of bone-targeted nanoparticles in OP treatment. Ongoing research into the development of targeted ligands and nanocarriers will continue to expand the possibilities of OP-targeted therapies into clinical application.

Targeted immunotherapy: harnessing the immune system to battle multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient's immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action underlying these immunotherapies. Specifically, we will explore the design of exosome-based bispecific monoclonal antibodies that offer cell-free immunotherapy options. The treatment landscape for myeloma continues to evolve with the development of numerous emerging immunotherapies. Given their significant advantages in modulating the MM immune environment through immune-targeted therapy, these approaches provide novel perspectives in selecting cutting-edge treatments for MM.

Brain-derived extracellular vesicles: Potential diagnostic biomarkers for central nervous system diseases.

Extracellular vesicles (EVs) are membrane-enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, and proteins, which can serve as biomarkers. Neurons and glial cells secrete EVs, contributing to various physiological and pathological aspects of brain diseases. EVs confer their role in the bidirectional crosstalk between the central nervous system (CNS) and the periphery owing to their distinctive ability to cross the unique blood-brain barrier (BBB). Thus, EVs in the blood, cerebrospinal fluid (CSF), and urine can be intriguing biomarkers, enabling the minimally invasive diagnosis of CNS diseases. Although there has been an enormous interest in evaluating EVs as promising biomarkers, the lack of ultra-sensitive approaches for isolating and detecting brain-derived EVs (BDEVs) has hindered the development of efficient biomarkers. This review presents the recent salient findings of exosomal biomarkers, focusing on brain disorders. We summarize highly sensitive sensors for EV detection and state-of-the-art methods for single EV detection. Finally, the prospect of developing advanced EV analysis approaches for the non-invasive diagnosis of brain diseases is presented.

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis.

Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide. Despite current treatments, the overall treatment outcome is unsatisfactory. Thus, patients with severe OA often require joint replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for preclinical and clinical palliation of OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules of the parental cells, including non-coding RNAs (ncRNAs) and proteins, have demonstrated a significant impact on the modulation of various physiological behaviors of cells in the joint cavity, making them promising candidates for cell-free therapy for OA. This review provides a comprehensive overview of the biosynthesis and composition of MSC-Exos and their mechanisms of action in OA. We also discussed the potential of MSC-Exos as a therapeutic tool for modulating intercellular communication in OA. Additionally, we explored bioengineering approaches to enhance MSC-Exos' therapeutic potential, which may help to overcome challenges and achieve clinically meaningful OA therapies.

Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform.

Exosomes have emerged as a promising cell-free therapeutic approach. However, challenges in large-scale production, quality control, and heterogeneity must be overcome before they can be used clinically. Biomimetic exosomes containing key components of natural exosomes have been assembled through extrusion, artificial synthesis, and liposome fusion to address these limitations. These exosome-mimetics (EMs) possess similar morphology and function but provide higher yields, faster large-scale production, and similar size compared to conventional exosomes. This article provides an overview of the chemical and biological properties of various synthetic exosome systems, including nanovesicles (NVs), EMs, and hybrid exosomes. We highlight recent advances in the production and applications of nanobiotechnology and discuss the advantages, limitations, and potential clinical applications of programming assembly of exosome mimetics.