Gold nanoparticles (AuNPs) exhibit promising potential in targeted drug delivery due to their unique structural features. Amongst them, anisotropic gold nanostars (AuNS) stand out for having heterogeneous mixture of star-shaped particles with variable branch numbers and lengths. AuNS demonstrate exceptional capability in projecting targeting molecules (such as Aptamers, Affibodies etc.) form their branches even in the presence of protein coronas.
A key focus of our lab is to design and evaluate novel nanoconstructs with enhanced receptor-targeting capabilities for developing targeted cancer therapeutics. For instance, our research demonstrates that AuNS with longer branches significantly outperform AuNPs with shorter or no branches in inducing targeted killing of HER2-overexpressing SKOV3 cancer cells in vitro when functionalized with HER2 targeting aptamers.
In addition to evaluating overall effectiveness of such receptor (e.g. HER2, nucleolin etc.) targeting nanoconstructs at the cellular level, we also moving forward to probe NP-receptor interactions at the single NP-level in real-time for comprehensive mechanistic insights, before testing their in vivo efficacies. We aspire to elucidate the intricate relationship between nanoparticle structure and their efficacy of targeted drug delivery, offering valuable insights for the development of more effective nanomedicines for the future.

Markers for various cancers have already been identified in exosomes. However, one major challenge of developing exosome-based diagnosis protocols is the rarity of cancer-specific exosomes in the body fluids, especially early in the disease. Alongside the cancer cells, all the healthy cells also produce exosomes, which would make the isolation and/or detection of cancer-specific exosomes extremely challenging. Any such detection approach that targets disease-specific exosomes, therefore needs to be extremely sensitive and selective towards the exosome of interest. In SERS, dramatic enhancements of Raman signals can occur selectively for molecules located on or near Gold or silver nanoparticle surfaces. This enables a high degree of selectivity and sensitivity in detecting molecule(s) of interest using SERS. One of the focus of our lab is to develop SERS-based technique to target and detect presence of exosomal protein and miRNA biomarkers in vitro.

Current diagnostics of Alzheimer's Disease (AD) typically probe the extent of neurodegeneration and/or plaque formation by Aβ-peptide molecules in brain, which is often too late for the implementation of any effective therapeutic interventions. We are in urgent need of alternative techniques that can flag the possibility of having AD, much early in the timeline of the disease progression. On the onset of AD, Aβ aggregates to form small-soluble oligomers. The concentrations of these oligomers in samples are expected to correlate well with the severity of the disease. Thus, probing the presence of Aβ oligomers in body fluids provides an attractive strategy for developing early diagnostics for AD. One major challenge, however, is that such oligomers are expected to be present in extremely low concentrations. Therefore, their detection would require highly sensitive techniques. We are currently working on developing SERS-based detection platforms for probing Aβ-oligomers in solution and in exosomes.

FCS is an optical technique known for its exceptional sensitivity, enabling the detection of analyte concentrations from femtomolar to micromolar levels. For instance, FCS has been used by us to investigate the interactions between fluorescently labeled lipophilic peptides and small unilamellar vesicles (SUVs), which are comparable in size to exosomes. Additionally, FCS has proven effective for the quantitative analysis of exosomes using DiI (a lipophilic fluorescent dye) and fluorescently labeled antibodies. FCS, therefore, has the potential to be employed for probing the presence of specific exosomal biomarkers, even at low concentrations. We aspire to use fluorescently tagged aptamers to target and probe the presence of specific exosomal biomarkers (e.g., HER2, miRNA etc.) in solution by FCS.