Antiviral therap
y using nucleoside reverse transcriptase inhibitors (NRTIs) is neurotoxic and has low efficienc
y in eradication of HIV-1 harbored in central nervous s
ystem (CNS). Previousl
y, we reported that active 5鈥?triphosphates of NRTIs encapsulated in cationic nanogels (nano-NRTIs) suppress HIV-1 activit
y more efficientl
y than NRTIs and exhibit reduced mitochondrial toxicit
y [Vinogradov SV,
Poluektova LY, Makarov E, Gerson T, Senana
yake MT. Nano-NRTIs: efficient inhibitors of HIV t
ype-1 in macrophages with a reduced mitochondrial toxicit
y.
Antivir Chem Chemother. 2010; 21:1-14. Makarov E, Gerson T, Senana
yake T, Poluektova LY, Vinogradov. Efficient suppression of Human Immunodeficienc
y Virus in Macrophages b
y Nano-NRTIs.
Antiviral Res. 2010; 86(1):A38-9]. Here, we demonstrated low neurotoxicit
y and excellent antiviral activit
y of nano-NRTIs decorated with the peptide (AP) binding brain-specific apolipoprotein E receptor. Nano-NRTIs induced lower levels of apoptosis and formation of reactive ox
ygen species, a major cause of neuron death, than free NRTIs. Optimization of size, surface decoration with AP significantl
y increased brain accumulation of nano-NRTIs. The efficient CNS deliver
y of nano-NRTIs resulted in up to 10-fold suppression of retroviral activit
y and reduced virus-associated inflammation in humanized mouse model of HIV-1 infection in the brain. Our data provide proof of the advanced efficac
y of nano-NRTIs as safer alternative of current antiviral drugs.
From the Clinical Editor
This team of investigators demonstrated low neurotoxicity and excellent anti-HIV activity of nano-nucleoside reverse transcriptase inhibitors decorated with the peptide (AP) binding brain-specific apolipoprotein E receptor, providing proof of enhanced efficacy and a safer alternative compared with current antiviral drugs.