Engineered exosomes for CRISPR/Cas delivery to overcome oncogene-driven drug resistance.

Engineered MSC-exosomes as CRISPR-Cas9 delivery vectors for precision immunotherapy

Mesenchymal stem cell-derived exosomes (MSC-Exos) combined with CRISPR-Cas9 hold substantial therapeutic potential for immune-mediated diseases, although significant technical obstacles remain. This review presents a comprehensive analysis of strategies for engineering MSC-Exos as delivery vehicles for CRISPR-Cas9, with emphasis on cargo-loading methodologies and surface modifications that enable targeting specific immune cell populations. We examine the mechanistic basis for the therapeutic effects of these engineered platforms and critically assess the challenges impeding clinical translation, including manufacturing scalability, safety concerns, and regulatory considerations. Key areas of focus for this Research Topic—vehicle engineering, cargo packaging efficiency, biological barriers, and in vivo safety—are systematically addressed. Finally, we discuss emerging directions, including next-generation gene editors and stimulus-responsive biomaterials. This review provides a balanced framework for advancing MSC-Exos-based nanoplatforms toward precision gene therapies for immune disorders.

Engineering CRISPR nanoplatforms to deplete cancer stem cells: Delivery checkpoints, target plasticity, and clinical viability.

Cancer stem cells (CSCs) sustain tumor initiation, therapy resistance, and relapse, yet evade durable control because they switch phenotype, enter quiescence, shelter within protective niches, resist drug efflux, and share markers with normal stem cells. Programmable CRISPR editing can disable intracellular self-renewal dependencies that antibodies and small molecules cannot reach, whereas only nanoscale carriers can confine such editing to intended cells; neither component alone solves the CSC problem. This review reframes CSC-directed CRISPR nanomedicine as an integrated design problem. We examine why target plasticity defeats static single-marker targeting; the sequential delivery checkpoints spanning blood stability, organ selection, tumor penetration, CSC recognition, endosomal escape, and productive editing; and advanced architectures including organ-selective lipid nanoparticles, biomimetic and vesicle carriers, metal-organic frameworks, and logic-gated systems. Genotoxicity, immunogenicity, incomplete depletion, manufacturing reproducibility, and absent CSC-specific clinical evidence remain limiting. Clinical viability, not imminent cure, is the realistic near-term objective.

Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes

Nanoparticle-Mediated CRISPR-Cas9 Delivery: Current Strategies, Pharmacological Challenges and Therapeutic Applications in Genetic Disorders

This review summarises the current strategies of nanoparticle-mediated CRISPR-Cas9 delivery, including lipid, polymeric, hybrid, inorganic, and biomimetic nanoparticles.

Engineered Exosomes as Next-generation Nanotherapeutics for Glioma: Crossing the Blood-brain Barrier Toward Precision Medicine.

BACKGROUND Glioma is one of the most aggressive and treatment-resistant malignancies of the central nervous system, characterized by rapid progression and poor prognosis. Conventional treatment approaches, including surgery, radiotherapy, and chemotherapy, often fail to achieve long-term remission due to the restrictive nature of the blood-brain barrier and the inherent heterogeneity of tumor cells. METHODS This review summarizes and critically analyzes current preclinical and clinical evidence on exosome biology, including their biogenesis, molecular cargo, and therapeutic engineering strategies. It further highlights recent advances in exosome-based delivery of chemotherapeutic agents, microRNAs, and gene-editing systems for glioma management. RESULTS Tumor- and stem cell-derived exosomes have demonstrated the ability to cross biological barriers while carrying functional biomolecules and modulating the tumor microenvironment. Their inherent stability, low immunogenicity, and capacity for surface modification make them promising nanocarriers for therapeutic applications. Engineered exosomes loaded with anti- tumor microRNAs, small interfering RNAs, or chemotherapeutic nanoparticles have shown promising results in enhancing drug sensitivity and reducing tumor proliferation in experimental glioma models. DISCUSSION The findings support the therapeutic potential of exosome-based platforms while also highlighting major challenges, including inconsistencies in isolation protocols, limited cargo- loading capacity, targeting specificity, and in vivo stability. Although exosomes have demonstrated the ability to overcome biological barriers and therapeutic resistance, standardized manufacturing protocols and robust clinical validation remain essential for successful clinical translation. CONCLUSION Exosome-based systems represent a promising approach for the diagnosis and treatment of glioma. Their dual role as biomarkers and therapeutic drug carriers offers significant potential for personalized medicine through non-invasive disease monitoring and targeted therapeutic strategies. However, further optimization of large-scale production, purification methods, and clinical translation is necessary before exosome-based therapeutics can be integrated into standard glioma treatment protocols.

Exosomes Next-Generation Approaches in Breast Cancer: Nano Drug Delivery to AI-Based Prediction

Exosome mimetic nanocarriers have risen as a progressive biomimetic approach for intracellular drug delivery, exploiting the unique properties of natural exosomes to enhance therapeutic precision and efficacy. These synthetic vesicles imitate the structural, biochemical, and functional characteristics of natural exosomes, including lipid bilayer composition, surface proteins, and molecular cargo, offering superior biocompatibility, immune evasion, and targeted delivery capabilities. Unlike traditional nanocarriers, exosome mimetics exploit receptor-mediated endocytosis and natural cellular communication pathways to facilitate efficient intracellular transport and controlled release of therapeutic payloads such as chemotherapeutic agents, nucleic acids(siRNA, miRNA, mRNA) and proteins. Engineering strategies combine advanced liposome technologies with exosomal components to overcome challenges of yield, scalability, and immunogenicity, enabling customizable and reproducible drug carriers. This chapter comprehensively reviews the design principles, fabrication methods, and functionalization techniques of exosome-mimetic nanocarriers, emphasizing their advantages in precision oncology. Mechanistic insights into cellular uptake, endosomal escape, and tumor targeting are comprehensive alongside preclinical studies demonstrating enhanced antitumor efficacy and safety profiles. Furthermore, the chapter discusses translational hurdles, including standardization, large-scale production, and regulatory considerations. Integration with emerging artificial intelligence tools and multiomics theranostics presents future opportunities for optimizing nanocarrier design, patient stratification, and treatment monitoring. Overall, exosome-mimetic nanocarriers represent a transformative strategy in nanomedicine, poised to revolutionize intracellular drug delivery and enable precision personalized therapy in breast cancer and beyond. Keywords: Exosome, breast cancer, exosome-biomimetic nanocarriers, intracellular drug delivery, cargo loading, targeted therapy.