modified-radical-neck-dissection-for-cervical-metastasis

Modified Radical Neck Dissection for Cervical Metastasis

Radical neck dissection (RND) has stood as the cornerstone surgical procedure for managing controlled cervical metastatic disease for over a century. This ...

Sichuan University

Using mass spectrometry-based high-throughput proteomics, we identified a membrane protein on extracellular vesicles (EVs), 90 K, which predicts poor overall survival of patients with head and neck cancer. 90 K levels in serum EVs could serve as an independent factor for poor prognosis of patients with head and neck cancer. Pre-treatment of immune competent mice with tumor-derived EVs (TDEs) elicited an immune-suppressive microenvironment for tumor cells, which was regulated by 90 K. The immunosuppressive function of TDE-90 K depends on the presence of myeloid derived suppressor cells (MDSCs) rather than regulatory T cells. The immune regulatory role of TDEs on MDSCs depends on miR-21 which is encapsulated in TDEs. Moreover, 90 K is required for the internalization of TDE cargo though interacting with integrin-β1 and anti-siglec-9 rather than directly affecting the immune function of MDSCs. 90 K modification of γδT cell-derived EVs (γδTEVs) could increase the delivery efficiency and therapeutic effect of PD-L1 siRNA by γδTEVs. We concluded that as a secreted protein modulating cell-cell and cell-matrix interactions, 90 K can be carried by TDEs to mediate the internalization and delivery of TDEs cargo by recipient cells. This function of 90 K could be utilized to improve the efficiency of EV-based drug delivery.

90 K increased delivery efficiency of extracellular vesicles through mediating internalization.

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules. Using a squamous cell carcinoma model, we demonstrated that a pH-sensitive fusogenic peptide -modification of BMSC-EVs achieved targetability in the microenvironment of a hypoxic tumor to deliver anti-tumor drugs. Using EGFR+HER2- and EGFR-HER2+ breast cancer models, we demonstrated that anti-EGFR and anti-HER2 modifications of BMSC-EVs were able to specifically deliver drugs to EGFR+ and HER2+ tumors, respectively. Using a collagen-induced arthritis model, we confirmed that anti-IL12/IL23-modified BMSC-EVs specifically accumulated in the arthritic joint and alleviated inflammation. Administration of SA-overexpressing BMSC-EVs has limited immunogenicity and high safety in vivo, suggesting that BMSC-derived EVs are ideal drug delivery vehicle. These representative scenarios of targeting modification suggest that, using different biotinylated molecules, the SA-overexpressing BMSC-EVs could be endowed with different targetabilities, which allows BMSC-EVs to serve as a versatile platform for targeted drug delivery under various situations.

Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery.

Corrigendum to '90 K increased delivery efficiency of extracellular vesicles through mediating internalization' [Journal of Controlled Release 353 (2023) 930-942].

Radiation-induced salivary gland injury is a common complication of radiotherapy for head and neck tumors. The traditional Chinese herbal compound Shengmai San (SMS) can regulate Qi-Yin deficiency, promote fluid secretion, and alleviate thirst. However, its therapeutic effects on radiation-induced salivary gland damage remain unexplored.

Article	Year
90 K increased delivery efficiency of extracellular vesicles through mediating internalization. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 36529385	2023
Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 37739016	2023
Corrigendum to '90 K increased delivery efficiency of extracellular vesicles through mediating internalization' [Journal of Controlled Release 353 (2023) 930-942]. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 41389377	2026
Shengmai San attenuates irradiation-induced salivary gland injury and fibrosis by inhibiting the SPHK1-S1P-S1PR1 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 41483577	2026

Hongxuan Wei

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