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].

Core Viewpoint - Cancer metastasis and recurrence remain the leading causes of cancer-related deaths, particularly in the lungs, necessitating new treatment strategies to improve outcomes for patients with lung metastases [2][5]. Group 1: CAR-T and CAR-M Therapies - CAR-T cell therapy has shown significant success in treating hematological malignancies, prompting ongoing trials for its application in solid tumors, despite challenges such as high cytotoxicity and insufficient tumor infiltration [2][3]. - CAR-M therapy is emerging as a promising candidate for cancer treatment due to its superior tumor infiltration and antigen-specific phagocytic capabilities, as well as its role as a specialized antigen-presenting cell [5]. Group 2: Research Findings - The recent study by the team at Sun Yat-sen University developed an inhalable engineered small extracellular vesicle (sEV) that delivers mRNA to generate CAR macrophages (CAR-M) in situ, effectively mitigating lung metastasis and preventing recurrence [3][11]. - Experimental results in mouse models demonstrated that inhaled CAR mRNA @aCD206 sEV accumulates in lung tissue, specifically delivering CAR mRNA to macrophages, thereby promoting the in situ generation of CAR-M cells and effectively inhibiting tumor growth while stimulating long-term memory immunity to prevent recurrence [9][11]. Group 3: Challenges and Innovations - Despite the potential of CAR-M therapy, challenges such as complex manufacturing processes and accumulation in the liver post-intravenous administration limit its broader application [6]. - The engineered sEV delivery platform developed in this research offers a promising new immunotherapy strategy to effectively combat lung metastasis and recurrence by selectively delivering CAR mRNA to macrophages in lung tissue [11].