Core Viewpoint - The research highlights the superior potential of small intracellular vesicles (sIV) over small extracellular vesicles (sEV) in drug delivery and retinal neuroprotection, suggesting a promising avenue for clinical applications in biomedical engineering [3][9][12]. Group 1: Research Findings - The study developed a method for isolating sIV from various cell types and demonstrated that sIV outperforms sEV in uptake, drug delivery, and retinal neuroprotection [3][7]. - sIV are smaller in size and yield higher quantities compared to sEV, exhibiting stronger cellular uptake capabilities in both in vitro and in vivo models [9]. - Molecular analysis revealed that sIV are enriched with endoplasmic reticulum and Golgi apparatus-related proteins, possessing unique microRNA characteristics associated with the intracellular membrane system, and contain higher levels of phospholipids such as phosphatidylcholine and phosphatidylethanolamine [9]. Group 2: Therapeutic Applications - sIV derived from mesenchymal stem cells (MSC) showed remarkable therapeutic effects in a retinal degeneration model by alleviating endoplasmic reticulum stress and delivering neuroprotective factors [9][11]. - The enhanced drug loading and delivery capabilities of sIV allow for effective transport of lipophilic compounds, such as rapamycin, to the retina [11]. Group 3: Implications for Clinical Translation - The findings indicate that sIV could serve as a promising alternative to traditional biological nanovesicles in clinical translation, potentially overcoming the limitations faced by sEV in therapeutic applications [12].