Parwana Krishma A K, Kaur Gill Priyapreet, Njanike Runyararo, Yiu Humphrey H P, Adams Chris F, Chari Divya Maitreyi, Jenkins Stuart Iain
School of Life Sciences, Keele University, Keele ST5 5BG, UK.
School of Medicine, Keele University, Keele ST5 5BG, UK.
Materials (Basel). 2024 May 14;17(10):2330. doi: 10.3390/ma17102330.
Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy. Here, primary mouse cortical microglia were cultured with a GFP-functionalized PODS for 24 h. Cell counts, cell morphology and Iba1 expression were all unaltered in treated cultures, indicating a lack of acute toxicity or microglial activation. Microglia exhibited internalisation of the PODS, with both cytosolic and perinuclear localisation. No evidence of adverse effects on cellular morphology was observed. Overall, 20-40% of microglia exhibited uptake of the PODS, but extracellular/non-internalised PODS were routinely present after 24 h, suggesting that extracellular drug delivery may persist for at least 24 h.
实现向中枢神经系统（CNS）的持续药物递送是神经损伤和疾病面临的一项重大挑战，目前正在开发各种递送载体来实现这一目标。自组装多角体蛋白晶体（多角体蛋白递送系统；PODS）正被用于递送治疗性蛋白质货物，并已在体内证明了其疗效。然而，为了确定PODS在神经应用中的效用，必须记录神经免疫细胞（小胶质细胞）对它们的处理情况，因为这些细胞会处理和降解许多生物材料，常常会阻碍治疗效果。在这里，将原代小鼠皮质小胶质细胞与绿色荧光蛋白功能化的PODS一起培养24小时。处理后的培养物中的细胞计数、细胞形态和Iba1表达均未改变，表明没有急性毒性或小胶质细胞激活。小胶质细胞表现出对PODS的内化，在细胞质和核周均有定位。未观察到对细胞形态有不利影响的证据。总体而言，20%-40%的小胶质细胞表现出对PODS的摄取，但24小时后通常会有细胞外/未内化的PODS存在，这表明细胞外药物递送可能会持续至少24小时。
