Polarization of macrophages to an anti-cancer phenotype through in situ uncaging of a TLR 7/8 agonist using bioorthogonal nanozymes.

Macrophages are plastic cells of the immune system that can be broadly classified as having pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes. M2-like macrophages are often associated with cancers and can promote cancer growth and create an immune-suppressive tumor microenvironment. Repolarizing macrophages from M2-like to M1-like phenotype provides a crucial strategy for anticancer immunotherapy. Imiquimod is an FDA-approved small molecule that can polarize macrophages by activating toll-like receptor 7/8 (TLR 7/8) located inside lysosomes. However, the non-specific inflammation that results from the drug has limited its systemic application. To overcome this issue, we report the use of gold nanoparticle-based bioorthogonal nanozymes for the conversion of an inactive, imiquimod-based prodrug to an active compound for macrophage re-education from anti- to pro-inflammatory phenotypes. The nanozymes were delivered to macrophages through endocytosis, where they uncaged pro-imiquimod in situ. The generation of imiquimod resulted in the expression of pro-inflammatory cytokines. The re-educated M1-like macrophages feature enhanced phagocytosis of cancer cells, leading to efficient macrophage-based tumor cell killing.

PREDICTING FOOT PROGRESSION ANGLE DURING GAIT USING TWO CLINICAL MEASURES IN HEALTHY ADULTS, A PRELIMINARY STUDY.

BACKGROUND: The foot progression angle (FPA) is related to the transverse plane rotation of the lower extremities and associated with many lower extremity conditions. PURPOSE: The purpose of this study was to examine how two commonly used clinical measures, tibio-fibular torsion (TF) and hip rotation, can be used to predict FPA during gait in healthy adults. STUDY DESIGN: Cross-sectional study design. METHODS: Passive hip internal and external rotation ranges of motion and TF torsion were measured with a 12-inch goniometer while the FPA (degree of toe-in/out) was measured with the GAITRite during midstance in sixty participants. The data was analyzed using a multiple regression model. RESULTS: Hip ER was not significant and was therefore excluded from the final model. The final model included passive hip IR and TF torsion (F = 19.64; p < .001; multiple R(2) = .41; adjusted R(2) = .39). Simple binary correlations showed that hip IR had a moderate negative correlation (r = -.40) with FPA (the greater the hip IR, the greater the in-toeing) while TF torsion had a positive correlation (r = .39) with FPA (the greater the external TF torsion. the greater the out-toeing). CONCLUSIONS: Greater amount of passive hip IR predicts in-toeing while greater TF torsion predicts out-toeing of the foot during midstance phase of gait. LEVEL OF EVIDENCE: Level 2.