Tuesday, May 9, 2023

PLGA-Maleimide from PolySciTech used in development of monocyte-targeting microparticles for use in Multiple Sclerosis treatment

 

One way to control drug delivery to specific locations is to affiliate the drug with cell type which traverses to that category so it can be carried along like the drugs are in a ‘backpack.’ This is particularly powerful for immune system treatment as immune cells provide for many opportunities of attachment based on signals and typically travel to sites of inflammation. Recently, researchers at Harvard University and Wyss Institute used PLGA-Maleimide (Cat# AI153) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create particles which surface adhere to monocytes and carry interleukin-4 and dexamethasone as immunomodulators. This research holds promise to provide treatment for Multiple sclerosis. Read more: Kapate, Neha, Michael Dunne, Ninad Kumbhojkar, Supriya Prakash, Lily Li-Wen Wang, Amanda Graveline, Kyung Soo Park et al. "A backpack-based myeloid cell therapy for multiple sclerosis." Proceedings of the National Academy of Sciences 120, no. 17 (2023): e2221535120. https://www.pnas.org/doi/abs/10.1073/pnas.2221535120

“Significance: Multiple sclerosis (MS) is a currently incurable autoimmune disease with a complex disease pathology. Despite the key role of myeloid cells in the pathophysiology of MS, current treatments do not specifically target myeloid cells or directly make their use for modulating the disease. We propose that immunomodulatory monocytes, upon intravenous injection, can infiltrate into inflamed central nervous system and have the potential to mitigate disease progression. We control monocyte phenotype through cell surface–adhered particles (“backpacks”) loaded with interleukin-4 and dexamethasone. Treatment with backpack-laden monocytes elicited local and systemic immunomodulatory effects, culminating in improved motor functions in experimental autoimmune encephalomyelitis mice. The results reported here demonstrate the possibility of myeloid cells as a therapy and drug target in MS. Abstract: Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS. We developed monocyte-adhered microparticles (“backpacks”) for activating myeloid cell phenotype to an anti-inflammatory state through localized interleukin-4 and dexamethasone signals. We demonstrate that backpack-laden monocytes infiltrated into the inflamed CNS and modulated both the local and systemic immune responses. Within the CNS, backpack-carrying monocytes regulated both the infiltrating and tissue-resident myeloid cell compartments in the spinal cord for functions related to antigen presentation and reactive species production. Treatment with backpack-monocytes also decreased the level of systemic pro-inflammatory cytokines. Additionally, backpack-laden monocytes induced modulatory effects on TH1 and TH17 populations in the spinal cord and blood, demonstrating cross talk between the myeloid and lymphoid arms of disease. Backpack-carrying monocytes conferred therapeutic benefit in EAE mice, as quantified by improved motor function. The use of backpack-laden monocytes offers an antigen-free, biomaterial-based approach to precisely tune cell phenotype in vivo, demonstrating the utility of myeloid cells as a therapeutic modality and target.”

Video:  https://youtu.be/OnndlGtOfKY

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