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• W3035941981 abstract "Abstract Activation of the immune system to treat cancer has emerged as a powerful therapy tool, however, treatments must overcome the immunosuppressive microenvironment established by tumors. Toll-like receptor (TLR) agonists like CpG and polyI:C are potent stimulators of non-specific, pro-inflammatory immune responses, targeting TLR9 and TLR3, respectively. While these immunostimulants seem promising, systemic exposure can eventually induce severe side effects. Adverse inflammatory reactions in healthy tissues may be avoided by delivering and retaining immunostimulants in proximity to tumors or to primary sites of tumor metastases. Immunostimulants such as CpG and polyI:C cannot be completely immobilized, however, since the target TLR9 and TLR3 are located intracellularly. Previously, polycations like poly- l -lysine (PLL) have been complexed to the anionic CpG or polyI:C with the purpose of improving intracellular delivery and potency. Here, the relationship between PLL molecular weight and immunostimulant complexation, TLR activation, and transport in a simple, model tumor microenvironment was investigated. The polyplexes could be formulated to dramatically limit immunostimulant transport suggesting the potential for injection site retention and minimized systemic exposure of immunostimulants. The molecular weight of PLL and ratio of PLL to immunostimulant affected the accessibility of the immunostimulant within the polyplex and polyplex interaction strength." @default.
• W3035941981 created "2020-06-25" @default.
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• W3035941981 date "2020-09-01" @default.
• W3035941981 modified "2023-10-17" @default.
• W3035941981 title "Immunostimulant Complexed With Polylysine Limits Transport and Maintains Immune Cell Activation" @default.
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• W3035941981 doi "https://doi.org/10.1016/j.xphs.2020.06.009" @default.
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