About

Andrew M. Smith is a Professor of Bioengineering at the University of Illinois Urbana-Champaign, holding the Donald Biggar Willett Faculty Scholar title. He earned his B.S. in Chemistry and Ph.D. in Bioengineering from Georgia Institute of Technology in 2002 and 2008, respectively. His research focuses on bio-micro and nanotechnology, with primary interests in cancer biology, intravital microscopy, live-cell imaging, nanomaterials, nanoparticle bioimaging probes, quantum dots, and single-molecule imaging. Smith has contributed to chapters in books on nanomedicine and nanotheranostics, and has published extensively in scientific journals on topics such as quantum dot synthesis, nanoparticle imaging, and targeted therapeutics. He is involved in multiple research initiatives related to cancer biology, molecular diagnostics, and targeted therapeutics, and holds faculty positions in the divisions of Nutritional Sciences, Medicine, and Technology Entrepreneurship at UIUC. His work emphasizes the development of advanced imaging techniques and nanomaterials for biomedical applications, particularly in cancer research and molecular diagnostics.

Research topics

• Materials science
• Optics
• Chemistry
• Optoelectronics
• Physics
• Computer Science
• Biology
• Biophysics
• Nanotechnology
• Biochemistry

Selected publications

• Nanocoding: Lipid Nanoparticle Barcoding for Multiplexed Single-Cell RNA Sequencing

  ACS Nano · 2025-06-09 · 3 citations

  articleOpen accessSenior authorCorresponding

  Sample multiplexing is an emerging method in single-cell RNA sequencing (scRNA-seq) that addresses high costs and batch effects. Current multiplexing schemes use DNA labels to barcode cell samples but are limited in their stability and extent of labeling of heterogeneous cell populations. Here, we describe nanocoding, a technology that applies lipid nanoparticles (LNPs) for high barcode labeling density in multiplexed scRNA-seq. LNPs reduce dependencies on cell surface labeling mechanisms due to multiple controllable means of cell uptake, amplifying barcode loading 10-100-fold and allowing both protection and efficient release by upon cell lysis. In cultured cell lines and heterogeneous cells from tissue digests, nanocoding occurs in 40 min with stability after sample mixing and requires only commercially available reagents without complex chemical modifications. In spleen digests, 6-plex barcoded samples show minimal unlabeled cells, with all barcodes giving bimodal count distributions. Challenging samples from adipose tissue of obese rodents containing lipid-rich debris and heterogeneous cells show more than 95% labeling with all known subtypes identified. Using nanocoding, we investigate gene expression changes related to aging in adipose tissue, profiling cells that could not be readily identified with current direct conjugate methods using lipid or antibody conjugates. The ease of generating and tuning these constructs may afford efficient and robust sample multiplexing with minimal crosstalk.

  PublisherOA PDFDOI

• Quantum Dot Encoding for In-Solution Single-Molecule Biomarker Counting in Metastatic Prostate Cancer

  medRxiv · 2025-11-04 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Digital assays are in wide development for biomarker quantification at the single-molecule level, but the common use of surface-pulldown steps limits both analytical sensitivity and throughput. Here, we develop surface-free, wash-free, in-solution assays with a sensitivity slope approaching unity for sequence-specific counting of microRNAs (miRs) relevant to metastatic castration-resistant prostate cancer (mCRPC). These assays are enabled by DNA nanoflowers (DNFs) densely encoded with ∼200 fluorescent quantum dots (QDs) that assemble in situ stoichiometrically to miRs. The QD-DNFs are detected as single events in solution by fluorescence microscopy or flow cytometry without washing away unbound labels. A ∼50 aM limit of detection and high agreement with absolute target count (0.95) were achieved by machine learning-guided assay optimization, providing the potential for calibration-free measurements. Multiple miR sequences could be distinguished through ratiometric and colorimetric (5-color) QD signatures with a single excitation source for flexible detection scenarios in static solution or flow streams. The assays were applied for detecting exosomal miRs from small-volume plasma of mCRPC patients and showed strong agreement with RT-qPCR, but with more reliable detection of the trace prognostic biomarker miR-375. Consistent with our prior reports using large volume blood draws, higher plasma levels of miR-375 were associated with poor survival of patients with mCRPC. We anticipate that in-solution absolute counting of clinical biomarkers in plasma will enable robust molecular analysis of trace biomarkers needed for the translation of cancer precision medicine.

  PublisherOA PDFDOI

• Nanomedicine targeting PPAR in adipose tissue macrophages improves lipid metabolism and obesity-induced metabolic dysfunction

  Science Advances · 2025-09-26 · 9 citations

  articleOpen accessSenior authorCorresponding

  Excess body fat leads to an overabundance of adipose tissue macrophages (AT MΦs) with altered phenotypes that play pathogenic roles in obesity comorbidities including diabetes and cancer. Peroxisome proliferator-activated receptors (PPARs) are leading targets to modulate AT MΦ phenotype. Here, we developed a dextran-based nanomedicine that delivers PPARα/γ agonists to AT MΦs and improves obesity and diabetic phenotypes in vivo. Within 1 week of treatment, AT MΦs decreased and became lipid laden, while extracellular vesicles secreted from AT decreased and reduced in lipid content. Within 2 weeks, glucose tolerance returned to levels of lean controls, followed by weight loss and reduced food intake. After 4 weeks, AT browning and amelioration of hepatic steatosis were evident. The physiological shifts were reproducible in three rodent models of obesity, spanning sexes and gonadal status. Effects were enhanced for the targeted nanomedicine compared with free drugs at equivalent doses, supporting the hypothesis that targeted PPAR activation in AT MΦs benefits systemic metabolism.

  PublisherDOI

• Internalization and Cellular Fate of Protein Corona‐Coated Nanoparticles by Multimodal Multi‐Scale Microscopy (Small 22/2025)

  Small · 2025-06-01

  articleOpen access

  Nanoparticles In article number 2409065, Mateus B. Cardoso and co-workers explore the intracellular fate of silica nanoparticles using multimodal microscopy. Cryogenic X-ray nanotomography and correlative fluorescence imaging reveal detailed nanoparticle trajectories from internalization to perinuclear localization, highlighting vesicle migration and fusion. These findings deepen our understanding of nanoparticle-cell interactions, supporting advancements in nanomedicine and drug delivery applications.

  PublisherOA PDFDOI

• MAPPING PATIENT-REPORTED OUTCOME MEASURES ACROSS CLINICAL TRIALS IN HEREDITARY ANGIOEDEMA (HAE)

  Annals of Allergy Asthma & Immunology · 2025-11-01 · 1 citations

  article
  PublisherDOI

• Dynamic Polymer Cross-linking Limits the Homogeneity of Compact Quantum Dots for Single-Particle Tracking

  ACS Applied Materials & Interfaces · 2025-08-29

  articleOpen accessSenior authorCorresponding

  Quantum dots (QDs) are semiconductor nanocrystals with stable and bright fluorescence, attributes particularly valued for single-molecule imaging in the life sciences. For these applications, QDs must be compact and homogeneously dispersed as single colloids, attributes enabled by multidentate polymer coatings. However, high-resolution analyses show evidence of clusters of two or more QDs (multimers) that may dominate measurements at the single-particle level. Here, we study the mechanisms of multimer formation using chromatographic separation, microscopy, spectroscopy, and affinity measurements. We find that multimers derive from dynamic polymer cross-linking and exist in a reversible state that is concentration-dependent and influenced by free polymers. Compared with monomers, QD multimers exhibit heterogeneous brightness, protein-induced aggregation, and enhanced nonspecific binding to cells, effects that bias single-particle measurements in live cells. Multimers can be depleted by purification, blocking desorbed binding groups on polymers, or increasing the net electrostatic charge. These findings provide solutions for improving nanocrystal quality for life science applications and point toward reporting standardizations of nanoparticle concentration and sample purity during characterization and application.

  PublisherOA PDFDOI

• Nanocrystal synthesis with alkoxy reagents for dispersion in polar and non-polar solvents

  Nature Synthesis · 2025-03-20 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Interdiffusion-enhanced cation exchange for HgSe and HgCdSe nanocrystals with infrared bandgaps

  Nature Synthesis · 2024-07-03 · 15 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Nanocrystal Synthesis with Alkoxy Ligands and Solvents

  ChemRxiv · 2024-01-30 · 1 citations

  preprintOpen accessSenior author

  Applications of colloidal nanocrystals in polar solvents often require nanocrystals synthesized in nonpolar solvents. However, solvent transfer processes are problematic and deteriorate nanocrystal quality. Here we report syntheses of nanocrystals with nearly universal solvent dispersibility using ligands and solvents with alkoxy repeating units. Core syntheses shell deposition, and cation exchange proceed similarly to traditional methods while products are more stable in aqueous solution than those generated by solvent transfer. (CdSe)CdZnS nanocrystals retain photoluminescence in cells for single-particle tracking experiments and outperform other nanocrystal classes in diffusion metrics reflecting stability and nonspecific binding. Distinct reaction classes yield nanocrystals with either methoxy or hydroxy ligand terminations, both of which can be purified by aqueous methods that are greener than traditional methods. These reactions can further generate nanocrystals with diverse compositions (oxides, sulfides, and selenides), shapes, and spectral bands with wide dispersibility that may make applications in polar solvents more widely accessible.

  PublisherOA PDFDOI

• Internalization and Cellular Fate of Protein Corona‐Coated Nanoparticles by Multimodal Multi‐Scale Microscopy

  Small · 2024-12-08 · 3 citations

  articleOpen access

  Upon exposure to biological environments, nanoparticles are rapidly coated with biomolecules, predominantly proteins, which alter their colloidal stability, biodistribution, and cell interactions. Despite extensive efforts to investigate the nanoparticles' fate, only a few studies use high-resolution characterization methods that allow in-depth characterization, and the existing methodologies are unable to differentiate particles internalized at the onset of incubation from those taken up toward the end of an incubation period. In this study, these limitations related to incubation disparities are overcame and precisely monitored the spatiotemporal displacement of colloidally stable protein corona-coated nanoparticles within cells. An unprecedented application of cryogenic X-ray nanotomography, combined with high-resolution, super-resolution, and correlative microscopy techniques, revealed the migration of nanoparticles to the perinuclear region while monitoring the evolution of cellular organelles in fully hydrated cells under near-native conditions, without the need for contrasting agents. Notably, this tracking indicates the progressive fusion of vesicles carrying the nanoparticles intracellularly. This strategy demonstrates the potential for uncovering the temporal aspects of nanoparticle behavior within cells and can be adaptable to a wide range of nanoparticles and cell types, offering a versatile and powerful tool to follow nanoparticles in cellular environments.

  PublisherOA PDFDOI

Recent grants

• Daily Quantification of Cancer-Associated Exosomal miRNA in Patient Blood by Photonic Crystal-Enhanced Quantum Dot Emission

  NIH · $1.0M · 2018–2024

• Hyperplexed Quantum Dots for Multidimensional Cell Classification in Intact Tissue

  NIH · $2.3M · 2021–2026

• I-Corps: Fluorescent Probes for Molecular Diagnostics

  NSF · $50k · 2017–2019

• NIH Grant F31DA018809

  NIH · $74k · 2007

• Super-Resolution Microscopy of Small Quantum Dots to Elucidate the Mechanisms of Alzheimer's Disease

  NIH · $3.3M · 2016–2022

Frequent coauthors

• Shuming Nie

  University of Illinois Urbana-Champaign

  99 shared

• T. P. Stecher

  76 shared

• R. C. Bohlin

  Space Telescope Science Institute

  70 shared

• R. W. O’Connell

  62 shared

• R. H. Cornett

  RTX (United States)

  33 shared

• M. S. Roberts

  Eureka Scientific

  32 shared

• Morton S. Roberts

  U.S. National Science Foundation

  31 shared

• S. G. Neff

  30 shared

Labs

• Smith LabPI

Education

• Ph.D., Biomedical Engineering

  Georgia Institute of Technology

  2008

• B.S., Chemistry

  Georgia Institute of Technology

  2002

Awards & honors

• Donald Biggar Willett Faculty Fellow (2020-Present)