Fig. 4: Long-term cell nanoparticle interactions. | Nature Communications

Fig. 4: Long-term cell nanoparticle interactions.

From: Transformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles

Fig. 4

Following a 10 µM (**P = 0.0026, ****P < 0.0001 NM1TFV vs. NM2TFV prodrug; **P = 0.0096 NM1TFV vs. NM2TFV TFV-DP) or b 100 µM treatments of NM1TFV (green), NM2TFV (orange) or TAF (blue) (**P = 0.001511, ***P = 0.000326, ***P = 0.000180, ****P < 0.0001 NM1TFV vs. NM2TFV prodrug on days 5, 10, 15, and 30, respectively; **P = 0.001911 NM1TFV vs. NM2TFV TFV-DP), intracellular prodrug (left) and TFV-DP (right) concentrations in MDM were measured over a 30-day period. Drug concentrations are expressed as mean ± SEM, N = 3 biological replicates. Following c, e 100 µM or d, f 10 µM treatments, the antiretroviral activities of NM1TFV and NM2TFV were determined by measures of HIV-1 RT activity in culture supernatants and by cell-associated HIV-1 p24 antigens by immunonocytochemistry. **P = 0.0042 NM1TFV vs. NM2TFV. e, f Scale bar: 100 μm. HIV-1 RT activity is expressed as mean ± SEM, N = 4 biological replicates. For comparison of two groups Student’s t-test (two-tailed, unpaired) was used (*P ≤ 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 NM1TFV compared with NM2TFV). A one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was used to compare the prodrug and TFV-DP levels among three treatment groups (*P ≤ 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 NM1TFV compared with NM2TFV).

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