Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease\'s progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

Tumors of the central nervous system (CNS) are severe and refractory diseases with poor prognosis, especially for patients with malignant glioblastoma and brain metastases. Currently, numerous studies have explored the potential role of bacteria and intestinal flora in tumor development and treatment. Bacteria can penetrate the blood-brain barrier (BBB), targeting the hypoxic microenvironment at the core of tumors, thereby eliminating tumors and activating both the innate and adaptive immune responses, rendering them promising therapeutic agents for CNS tumors. In addition, engineered bacteria and derivatives, such as bacterial membrane proteins and bacterial spores, can also be used as good candidate carriers for targeted drug delivery. Moreover, the intestinal flora can regulate CNS tumor metabolism and influence the immune microenvironment through the \"gut-brain axis\". Therefore, bacterial anti-tumor therapy, engineered bacterial targeted drug delivery, and intervention of the intestinal flora provide therapeutic modalities for the treatment of CNS tumors. In this paper, we performed a comprehensive review of the mechanisms and therapeutic practices of bacterial therapy for CNS tumors and discussed potential future research directions in this field.

Nanoengineering has emerged as a progressive method in cancer treatment, offering precise and targeted delivery of therapeutic agents while concurrently reducing overall toxicity. This scholarly article delves into the innovative strategies and advancements in nanoengineering that bridge the gap between clinical practice and research in the field of cancer treatment. Various nanoengineered platforms such as nanoparticles, liposomes, and dendrimers are scrutinized for their capacity to encapsulate drugs, augment drug efficacy, and enhance pharmacokinetics. Moreover, the article investigates research breakthroughs that drive the progression and enhancement of nanoengineered remedies, encompassing the identification of biomarkers, establishment of preclinical models, and advancement of biomaterials, all of which are imperative for translating laboratory findings into practical medical interventions. Furthermore, the integration of nanotechnology with imaging modalities, which amplify cancer detection, treatment monitoring, and response assessment, is thoroughly examined. Finally, the obstacles and prospective directions in nanoengineering, including regulatory challenges and issues related to scalability, are examined. This underscores the significance of fostering collaboration among various entities in order to efficiently translate nanoengineered interventions into enhanced cancer therapies and patient management.

Glioblastoma, a formidable brain cancer, has remained a therapeutic challenge due to its aggressive nature and resistance to conventional treatments. Recent data indicate that aptamers, short synthetic DNA or RNA molecules can be used in anti-cancer therapy due to their better tumour penetration, specific binding affinity, longer retention in tumour sites and their ability to cross the blood-brain barrier. With the ability to modify these oligonucleotides through the selection process, and using rational design to modify them, post-SELEX aptamers offer several advantages in glioblastoma treatment, including precise targeting of cancer cells while sparing healthy tissue. This review discusses the pivotal role of aptamers in glioblastoma therapy and diagnosis, emphasising their potential to enhance treatment efficacy and also highlights recent advancements in aptamer-based therapies which can transform the landscape of glioblastoma treatment, offering renewed hope to patients and clinicians alike.

Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs\' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs\' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.

Probiotics are live microorganisms that inhabit the gastrointestinal tract and confer health benefits to consumers. However, a sufficient number of viable probiotic cells must be delivered to the specific site of interest in the gastrointestinal tract to exert these benefits. Enhanced viability and tolerance to sublethal gastrointestinal stress can be achieved using appropriate coating materials and food matrices for orally consumed probiotics. The release mechanism and interaction of probiotic microcapsules with the gastrointestinal tract have been minimally explored in the literature to date. To the authors\' knowledge, no review has been published to discuss the nature of release and the challenges in the targeted delivery of probiotics. This review addresses gastrointestinal-related complications in the formulation of targeted delivery and controlled release of probiotic strains. It investigates the impacts of environmental stresses during the transition stage and delivery to the target region in the gastrointestinal tract. The influence of factors such as pH levels, enzymatic degradation, and redox conditions on the release mechanisms of probiotics is presented. Finally, the available methods to evaluate the efficiency of a probiotic delivery system, including in vitro and in vivo, are reviewed and assessed. The paper concludes with a discussion highlighting the emerging technologies in the field and emphasising key areas in need of future study.

Bioorthogonal reactions have revolutionized chemical biology by enabling selective chemical transformations within living organisms and cells. This review comprehensively explores bioorthogonal chemistry, emphasizing inverse-electron-demand Diels-Alder (IEDDA) reactions between tetrazines and strained dienophiles and their crucial role in chemical biology and various applications within the human body. This highly reactive and selective reaction finds diverse applications, including cleaving antibody-drug conjugates, prodrugs, proteins, peptide antigens, and enzyme substrates. The versatility extends to hydrogel chemistry, which is crucial for biomedical applications, yet it faces challenges in achieving precise cellularization. In situ activation of cytotoxic compounds from injectable biopolymer belongs to the click-activated protodrugs against cancer (CAPAC) platform, an innovative approach to tumor-targeted prodrug delivery and activation. The CAPAC platform, relying on click chemistry between trans-cyclooctene (TCO) and tetrazine-modified biopolymers, exhibits modularity across diverse tumor characteristics, presenting a promising approach in anticancer therapeutics. The review highlights the importance of bioorthogonal reactions in developing radiopharmaceuticals for positron emission tomography (PET) imaging and theranostics, offering a promising avenue for diverse therapeutic applications.