Self-Fluorescent Lone Tryptophan Nanoparticles as Theranostic Agents Against Alzheimer’s Disease
Manju Sharma, Virendra Tiwari, Swati Chaturvedi, Muhammad Wahajuddin, Shubha Shukla, Jiban Jyoti Panda
Abstract
Aggregation of β-amyloid (Aβ42) peptide in the neural extracellular space leads to cellular dysfunction, resulting in Alzheimer's disease (AD). The hydrophobic core of the amyloidogenic Aβ42 peptide contains aromatic residues that play an important role in the self-assembly and subsequent aggregation of the peptide. Hence, targeting these hydrophobic core residues by potent low molecular agents can be a promising therapeutic approach toward AD. In the current work, we have developed self-fluorescent solo tryptophan nanoparticles (TNPs) as nanotheranostic systems against AD. We demonstrated that TNPs could significantly inhibit as well as disrupt the fibrils formed by both Aβ42 peptide and another reductionist approach-based amyloid model dipeptide, phenylalanine-phenylalanine (FF). More importantly, these nanostructures were nontoxic to neural cells and could protect the neurons from Aβ42 peptide and FF aggregate-induced cytotoxicity. In addition, efficacy studies performed in animal model further revealed that the TNPs could rescue spatial and learning memory in intracerebroventricular streptozotocin-administration-induced AD phenotype in rats. Moreover, our pharmacokinetics study further established the BBB permeability and brain delivery potency of TNPs. The inherent excellent fluorescent properties of these nanoparticles could be exploited further to use them as imaging modalities for tagging and detecting FF and Aβ42 peptide fibrils. Overall, our results clearly illustrated that the solo TNPs could serve as promising nanotheranostic agents for AD therapy.