Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells

Parwana, Krishma A. K.; Kaur Gill, Priyapreet; Njanike, Runyararo; Yiu, Humphrey H. P.; Adams, Chris F.; Chari, Divya Maitreyi; Jenkins, Stuart Iain

Abstract

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.

Citation

Parwana, K. A. K., Kaur Gill, P., Njanike, R., Yiu, H. H. P., Adams, C. F., Chari, D. M., & Jenkins, S. I. (in press). Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells. Materials, 17(10), Article 2330. https://doi.org/10.3390/ma17102330

• Journal Article Type: Article
• Acceptance Date: Apr 26, 2024
• Online Publication Date: May 14, 2024
• Deposit Date: May 28, 2024
• Journal: Materials
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 10
• Article Number: 2330
• DOI: https://doi.org/10.3390/ma17102330
• Public URL: https://keele-repository.worktribe.com/output/833337
• Publisher URL: https://www.mdpi.com/1996-1944/17/10/2330