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Figure 8. Application of active loading and hybrid-engineering strategies for exosome-mediated drug delivery. (A-F) Electroporation-based loading of miR-195-5p into extracellular vesicles (miR-195 eEVs) for melanoma treatment sensitization, including particle-size distribution, miRNA-loading validation, intratumoral administration, VEGFA modulation, measurable tumor-free rate, and tumor-volume evaluation. *P < 0.05, **P < 0.01, ***P < 0.001, Reprinted with permission^[190]. Copyright 2023, MDPI. (G-J) Ultrasound-mediated drug delivery system using a customized convex acoustic lens-attached ultrasound (CALUS) platform for enhanced antitumor efficacy in a murine melanoma subcutaneous model, including in vitro system design, microbubble-intensity reduction, MRI assessment, tumor growth, and body-weight changes. ****P < 0.0001, Reprinted with permission^[191]. Copyright 2023, Elsevier. (K-N) Cross-tumor example of exosome-liposome hybrid nanoparticles (HENPs) co-delivering triptolide (TP) and miR497, including hybrid-vesicle construction, ultrastructural characterization, particle-size/fluorescence characterization, and apoptosis assessment. Reprinted with permission^[183]. Copyright 2022, Springer Nature. CALUS: Convex acoustic lens-attached ultrasound; eEVs: engineered extracellular vesicles; HENPs: hybrid exosome-liposome nanoparticles; MRI: magnetic resonance imaging; TP: triptolide; VEGFA: vascular endothelial growth factor A.