Namita Rajesh Nabar

All Publications

• Systematic engineering of Layer-by-Layer anti-miR coated wound dressings with tunable release kinetics BIOMATERIALS ADVANCES Berger, A. G., Vo, C., Kaskow, J. A., Rawal, S., Cai, E., Deiss-Yehiely, E., Nabar, N., Dacoba, T. G., Marand, M., Park, J., Covarrubias, G., DeLorenzo, C., Feinberg, M. W., Hammond, P. T. 2026; 188: 215064

  Abstract

  The Layer-by-Layer (LbL) technique enables conformal coating of commercial wound dressings with oligonucleotide therapeutics and polymeric excipients to achieve controlled delivery to non-healing wounds. We previously demonstrated a proof-of-concept LbL dressing containing miRNA inhibitors (anti-miRs); however, release occurred on a single time scale. Because wound healing is dynamic, temporally tuning anti-miR delivery to the wound may alter therapeutic effects. Here, we provide an approach to modulate oligonucleotide release kinetics from coated wound dressings, exploring the design space of excipients, formulation parameters, and oligonucleotide structure. Incorporation of Laponite nanoclay prolonged release, while poly(acrylic acid) accelerated release kinetics. Hydrolyzable poly(β-amino esters) with varying hydrolysis rates were also used to further tune release kinetics. A fast-release formulation demonstrated 40% release over 4 h, while a slow-release formulation took 24 h to release the same amount. We evaluated these dressings in an excisional chronic wound model in diabetic (db/db) mice using anti-miR-92a (92ai), selected for its ability to enhance angiogenic signaling and promote wound closure. Dressings coated with 92ai accelerated healing compared to non-targeting scramble anti-miR (Scr) controls, with closure rates accelerated at times corresponding to release kinetics. Although ultimate wound closure was similar across release conditions, analyses of gene expression, cellular composition, histology, and immunofluorescence suggested distinct underlying mechanisms. Differences were particularly evident in macrophage phenotype and angiogenesis, suggesting that release timing influences biological pathways active during repair. Overall, these findings demonstrate that LbL dressings can be engineered for temporally controlled oligonucleotide delivery and that release kinetics may shape mechanisms driving wound closure.

  View details for DOI 10.1016/j.bioadv.2026.215064

  View details for Web of Science ID 001827982800001

  View details for PubMedID 42470818

• Subcellular nanoparticle trafficking investigated with label-free, live cell imaging NANOSCALE HORIZONS Nelson, E. B., Covarrubias, G., Nabar, N., Gomerdinger, V. F., Scott, A., Hammond, P. T., Straehla, J. P. 2026; 11 (4): 1011-1021

  Abstract

  Nanoparticle drug delivery systems have significant potential to transform precision medicine due to their ability to encapsulate a wide range of cargo, improve systemic circulation time, and enhance targeted delivery. These delivery properties can be further modified by altering the surface chemistry of the nanoparticle carrier. However, a gap remains in our understanding of the cellular mechanisms underlying nanoparticle uptake, in addition to the subcellular trafficking kinetics. A comprehensive understanding of nanoparticle-cell interactions considering both the nanocarrier and the drug cargo has been challenging, in part due to technological limitations. Here, we present a robust imaging workflow to study long-term dynamics of nanoparticle delivery in live cells. We show that integration of holography and tomography enhances the study of live cells in a label-free environment and can be combined with intermittent fluorescence microscopy to assess nanoparticle uptake and delivery kinetics for up to 30 hours. We also describe a method to quantitatively characterize uptake of a library of fluorescently tagged lipid- and polymer-based nanoformulations without introducing cell or organelle markers. This application of dynamic fluorescent holotomography as a novel method to investigate nanoparticle uptake and cargo delivery highlights the expanding utility of multimodal, label-free, live imaging techniques.

  View details for DOI 10.1039/d5nh00749f

  View details for Web of Science ID 001693165600001

  View details for PubMedID 41705321

  View details for PubMedCentralID PMC12914502

• Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery SCIENCE Boehnke, N., Straehla, J. P., Safford, H. C., Kocak, M., Rees, M. G., Ronan, M., Rosenberg, D., Adelmann, C. H., Chivukula, R. R., Nabar, N., Berger, A. G., Lamson, N. G., Cheah, J. H., Li, H., Roth, J. A., Koehler, A. N., Hammond, P. T. 2022; 377 (6604): 384-+

  Abstract

  To accelerate the translation of cancer nanomedicine, we used an integrated genomic approach to improve our understanding of the cellular processes that govern nanoparticle trafficking. We developed a massively parallel screen that leverages barcoded, pooled cancer cell lines annotated with multiomic data to investigate cell association patterns across a nanoparticle library spanning a range of formulations with clinical potential. We identified both materials properties and cell-intrinsic features that mediate nanoparticle-cell association. Using machine learning algorithms, we constructed genomic nanoparticle trafficking networks and identified nanoparticle-specific biomarkers. We validated one such biomarker: gene expression of SLC46A3, which inversely predicts lipid-based nanoparticle uptake in vitro and in vivo. Our work establishes the power of integrated screens for nanoparticle delivery and enables the identification and utilization of biomarkers to rationally design nanoformulations.

  View details for DOI 10.1126/science.abm5551

  View details for Web of Science ID 000830834600029

  View details for PubMedID 35862544

  View details for PubMedCentralID PMC10249039