Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Platelet Disorders/chemically induced ; Child ; Child, Preschool ; Contrast Media/*adverse effects/diagnostic use ; Databases, Factual ; Female ; Humans ; Infant ; Infant, Newborn ; Iodine Radioisotopes/chemistry ; Male ; Middle Aged ; Neoplasms/radionuclide imaging ; Radiopharmaceuticals/*adverse effects/diagnostic use ; Urologic Diseases/chemically induced ; Young Adult