biostudies-literatureZhang HNational Cancer InstituteNCI NIH HHS1080-1094https://www.ebi.ac.uk/biostudies/studies/S-EPMC7906914biostudies-literatureUnknown330Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. R848 was remotely loaded into TSLs composed of DPPC: DSPC: DSPE-PEG2K (85:10:5, mol%) with 100 mM FeSO₄ as the trapping agent inside. The final R848 to lipid ratio of the optimized R848-loaded TSLs (R848-TSLs) was 0.09 (w/w), 10-fold higher than the previously-reported values. R848-TSLs released 80% of R848 within 5 min at 42 °C. These TSLs were then combined with αPD-1, an Journal of controlled release : official journal of the Controlled Release SocietyDevelopment of thermosensitive resiquimod-loaded liposomes for enhanced cancer immunotherapy.PMC7906914R01 CA211602R01 CA210553R01 CA250557R01 CA112356R01 CA253316Tang WLFerrara KWFoiret JMahakian LMBaikoghli MZhang HBorowsky ADWu BRaie MNCheng RHFite BZLau KKheirolomoom ATam SMIngham ESTumbale SKfalseDevelopment of thermosensitive resiquimod-loaded liposomes for enhanced cancer immunotherapy.Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. R848 was remotely loaded into TSLs composed of DPPC: DSPC: DSPE-PEG2K (85:10:5, mol%) with 100 mM FeSO₄ as the trapping agent inside. The final R848 to lipid ratio of the optimized R848-loaded TSLs (R848-TSLs) was 0.09 (w/w), 10-fold higher than the previously-reported values. R848-TSLs released 80% of R848 within 5 min at 42 °C. These TSLs were then combined with αPD-1, an 2021-01-01T00:00:00Z2021 Feb2025-04-04T19:53:54.672Z2025-04-04T19:53:54.672ZS-EPMC79069143318978610.1016/j.jconrel.2020.11.013