Towards nanomedicines for neuroAIDS.

Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remain a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. Thus, development of target-specific, effective, safe, and controllable drug-delivery approach is an important health priority for global elimination of AIDS progression. Emergence of nanotechnology in medicine has shown exciting prospect for development of novel drug delivery systems to administer the desired therapeutic levels of ARV drugs in the CNS. Neuron-resuscitating and/or antidependence agents may also be delivered in the brain through nanocarriers to countercheck the rate of neuronal degradation during HIV infection. Several nanovehicles such as liposomes, dendrimers, polymeric nanoparticles, micelles, and solid lipid nanoparticles have been intensively explored. Recently, magnetic nanoparticles and monocytes/macrophages have also been used as carrier to improve the delivery of nanoformulated ARV drugs across the blood-brain barrier. Nevertheless, more rigorous research homework has to be elucidated to sort out the shortcomings that affect the target specificity, delivery, release, and/or bioavailability of desired amount of drugs for treatment of neuroAIDS.

DNA aptamers that bind to PrP(C) and not PrP(Sc) show sequence and structure specificity.

DNA aptamers were selected against recombinant human (rhu) cellular prion protein (PrP(C)) 23-231 by systematic evolution of ligands via a systematic evolution of ligands by exponential (SELEX) enrichment procedure using lateral flow chromatography. The SELEX procedure was performed with an aptamer library consisting of a randomized 40-nucleotide core flanked by 28-mer primer-binding sites that, theoretically, represented approximately 10(24) distinct nucleic acid species. Sixty nanograms of rhuPrP(C)23-231 immobilized in the center of a lateral flow device was used as the target molecule for SELEX. At the end of 6 iterations of SELEX, 13 distinct candidate aptamers were identified, of which, 3 aptamers represented 32%, 8%, and 5% of the sequences respectively. Eight aptamers, including the three most frequently occurring candidates, were selected for further evaluation. Selected aptamers bound to rhuPrP(C)23-231 at 10(-6) M to 10(-8) M concentrations. Two of the eight aptamers bound at higher concentrations to rhuPrP(C)90-231. Theoretical thermodynamic modeling of selected aptamer sequences identified several common motifs among the selected aptamers that could play a role in PrP binding. Binding affinity to rhuPrP(C)23-231 was both aptamer sequence and structure dependent. Further, selected aptamers bound to mammalian PrPs derived from brain of healthy sheep, calf, piglet, and deer, and to PrP(C) expressed in mouse neuroblastoma cells. None of the aptamers bound to proteinase K-digested scrapie-infected mouse neuroblastoma cells or untreated PrP-null cells, which further confirmed the PrP(C) specificity of the aptamers. In summary, we enriched and selected DNA aptamers that bind specifically to rhuPrP(C) and mammalian PrP(C) with varying affinities and can be applied to biological samples for PrP(C) enrichment and as diagnostic tools in double ligand assay systems.