About

Professor Vincent M. Rotello is a principal investigator in the Rotello Research Group, with a focus on interactions in chemistry. His research encompasses areas such as antimicrobials, bioorthogonal chemistry, drug delivery, and sensing. He is recognized as a top researcher globally and has delivered plenary talks at major conferences such as the ACS Fall 2025. His work is dedicated to advancing understanding and innovation in chemical interactions, contributing significantly to the fields of chemical biology and materials science.

Research topics

• Nanotechnology
• Biology
• Materials science
• Microbiology
• Cancer research
• Oncology
• Computational biology
• Chemistry
• Medicine
• Internal medicine

Selected publications

• Precision payloads: enhancing potency and selectivity

  Bioconjugation Insights · 2026-04-29

  article1st authorCorresponding

  “We are now in the process of swinging from the importance of chemistry to the importance of biology.”Bioconjugate Insights brings together perspectives from Vincent Rotello, David Thurston, and Christian Marsolais to explore emerging technologies and design principles that are defining the future of payload optimization, and by extension, the future growth of the bioconjugation field.

  PublisherDOI

• Hyaluronic acid-coated polymer-siRNA nanovectors for evading macrophage uptake and STAT3 gene silencing in breast cancer cells

  Cambridge Materials Health · 2026-04-10

  articleSenior author
  PublisherDOI

• Mechanistic insights into hydrophobicity-dependent antimicrobial selectivity of quaternary ammonium poly(oxanorborneneimide) polymers using coarse-grained simulations

  DRYAD · 2026-04-01

  datasetOpen access

  The rise of antibiotic resistance to small-molecule drugs has driven the development of materials that directly disrupt bacterial cell membranes. Inspired by antimicrobial peptides (AMPs), synthetic polymers are gaining attention as promising antimicrobial materials because their molecular properties can be tuned to enhance selective killing of bacterial versus mammalian cells. Poly(oxanorborneneimide) (PONI) polymers have exhibited high selectivity against a broad spectrum of bacteria over human cells, depending upon their side chain functionalities. However, the mechanistic basis of this selectivity remains poorly understood, limiting the design of new PONI polymers with enhanced selectivity. In this study, we present a molecular dynamics (MD) simulation framework to investigate PONI-membrane interactions and extract mechanistically relevant descriptors correlated with experimentally determined activities. We model four PONI polymers with side chains of increasing hydrophobicity to understand interactions with model E. coli, methicillin-resistant S. aureus (MRSA), and human red blood cell (RBC) membranes. We develop a generalizable coarse-grained parameterization strategy for PONI polymers within the MARTINI 3 force field to enable simulation of polymer-membrane interactions at relevant length and timescales. Our simulations reveal that experimental activities against different membranes can be related to the propensity for PONI polymers to insert into the membrane, driven by electrostatic and hydrophobic interactions. We find that differences in membrane composition, particularly enrichment of cardiolipin in bacterial membranes, play a critical role in the selective interactions of moderately hydrophobic polymers toward bacterial membranes, in contrast with the non-selective toxicity toward both bacterial and RBC membranes observed for highly hydrophobic polymers.

  PublisherDOI

• Targeting bacterial biofilms using polymer-stabilized nanoemulsions

  Expert Opinion on Drug Delivery · 2025-09-22 · 1 citations

  reviewSenior authorCorresponding

  INTRODUCTION: Antimicrobial resistance (AMR) in bacterial infections is a critical global health threat, contributing significantly to increased morbidity and mortality. This challenge is further amplified by biofilms that act as a protective barrier around bacteria, limiting the effective action of antibiotics and host immune responses. AREAS COVERED: This review highlights the potential of nanoemulsion (NE) systems in delivering hydrophobic payloads, particularly essential oils (EOs), into biofilms, negatively charged extracellular polymeric substance (EPS) matrix. While essential oils exhibit strong antimicrobial properties, their effectiveness against biofilms is restricted due to poor bioavailability and limited biofilm penetration. EXPERT OPINION: NE systems employing natural, semisynthetic, and synthetic polymeric scaffolds offer an effective delivery method for EOs, enabling enhanced penetration into the negatively charged EPS matrix of biofilms. These therapeutics have significant potential for treating refractory biofilm-related AMR infections.

  PublisherDOI

• Targeting Airway Remodeling Via Polymer Nanoparticles

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract Rationale : Airway remodeling in asthma involves increased airway smooth muscle (ASM) mass, changes to bronchial epithelial cell (BEC) layer, and increased fibrosis. ASM and BECs actively contribute by secreting growth factors and cytokines, regulating extracellular matrix (ECM) composition and enhancing cell proliferation/migration. Altering mechanisms which modulate remodeling presents a key to novel therapeutic strategies. BDNF increases ASM [Ca2+]i and contractility, and potentiates the effects of inflammation. Importantly, studies show that ASM is not only a target, but also a source of BDNF, raising the possibility of local autocrine/paracrine effects. Arginase 1 and 2 are expressed by BECs, but their roles in asthma are still under investigation with studies showing arginase 1 inhibition blunting epithelial remodeling and ASM hyperplasia. Knockdown of appealing targets such as ASM BDNF and epithelial arginases using small interfering RNA (siRNA) is a promising approach to combating inflammatory lung remodeling. Polymer based nanoparticles have been constructed which demonstrate cell-type specificity and high efficiency in delivering siRNA. Thus, we hypothesize that BDNF and arginases are central to airway remodeling and can be targeted via nanopartiacles.Methods: Primary human ASM and BEC cells from non-asthmatic vs. asthmatic individuals were obtained post-surgery from lung tissues after approval Mayo Clinic IRB. PONI-Guan NP were generated using block copolymer engineering. PCR, immunoblotting and ELISA were performed using standard techniques. Contractility studies were conducted in adult mouse precision cut lung slices. In vivo lung function studies were conducted in 6-8 week old mice, with or without mixed allergen (MA) treatment and Scireq Flexivent system. Results: PONI-Guan NP uptake demonstrates cell-type specificity in BEC/ASM co-culture and mouse lung. Arginase I/II and ECM expression is upregulated in BECs when exposed to BDNF and cytokines. In ASM, BDNF is increased in asthmatics compared to non-asthmatic controls; ECM expression is increased in response to BDNF and TNF-α. In BEC, PONI-Guan NP/siRNA inhibits Arg I/II expression, even in the presence of TNF-α. In ASM, TNF-α increases in BDNF secretion and ECM deposition are blunted by NP-delivered siRNA. PCLS and mouse lung function studies show contractility to MCh: effects suppressed by NP-delivered BDNF and Arg I siRNA. Conclusions: Our studies show the importance of BDNF/Arginase pathways in airway remodeling and efficacy of PONI-based siRNA delivery vectors in blunting remodeling processes.

  PublisherDOI

• Mass Spectrometry Imaging Reveals That Gold Nanomaterial Surface Chemistry Affects Transport and Excretion in Mice over Time

  Chemical & Biomedical Imaging · 2025-01-03 · 4 citations

  articleOpen access

  , especially as they interact with the immune system and excretory organs, to ensure their efficacy, safety, and clearance. Here, we demonstrate the unique capabilities of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging for revealing the temporal redistribution of gold NPs (AuNPs) in key excretory organs. The quantitative and suborgan specific information available in LA-ICP-MS measurements indicate that positive AuNPs are more rapidly excreted through the hepatobiliary system of the liver than AuNPs having other surface charges. Using multielement image segmentation methods, we find that positive and zwitterionic AuNPs transition from the marginal zone of the spleen to the red pulp over time, indicating uptake by red pulp macrophages. In contrast, negative AuNPs redistribute more slowly, indicating different interactions with the immune system. Comparisons of high-resolution LA-ICP-MS images and fluorescence microscopy images on the same tissue sections reveal that positive AuNPs are excreted through the glomeruli of the kidney more effectively than are AuNPs with other charges. Overall, we demonstrate the power of LA-ICP-MS imaging for providing detailed information about AuNP fate at the suborgan level, which affords new insight into the interplay between surface chemistry and excretion pathways.

  PublisherDOI

• Array-based polymer-phage biosensors for detection and differentiation of bacteria

  Sensors & Diagnostics · 2025-01-01 · 2 citations

  articleOpen accessSenior author

  (MSSA) and MRSA) with high classification accuracy (94-100%) and correct unknown identification rates (94-100%) under optimized conditions. By leveraging phage-host interactions and polymer binding properties, the polymer-phage sensor overcomes the limitations of traditional "lock-and-key" biosensors, offering enhanced specificity and reliability. This platform's rapid response time and adaptability make it a promising tool for clinical diagnostics and public health applications, particularly in combating antibiotic-resistant bacteria.

  PublisherOA PDFDOI

• Breaking the cellular delivery bottleneck: recent developments in direct cytosolic delivery of biologics

  RSC Pharmaceutics · 2025-01-01 · 7 citations

  reviewOpen accessSenior author

  Proteins and nucleic acid therapeutics represent a significant and growing share of the pharmaceutical landscape. The majority of biological and therapeutic applications of these biomolecules require access to the cytosol. Delivery of biologics directly to the cytosol is made difficult by the impermeability of the cell membrane. As a result, most delivery strategies have utilized endocytic uptake pathways to deliver biologics into the cell. However, endosomally entrapped cargo often faces limited escape efficiency and is prone to degradation within endo/lysosomal compartments. The emergence of delivery vehicles capable of bypassing endocytosis and directly traversing the cell membrane offers a promising approach to improve the cytosolic delivery efficiency of biomolecules. Here, we highlight recent developments in endocytosis-independent delivery systems for biologics and ways to accurately assess cytosolic delivery of biologics. Strategies employing covalent and non-covalent modification of biomolecules will be reviewed, along with strategies incorporating both covalent and supramolecular processes.

  PublisherOA PDFDOI

• Engineered Lipid Coronas for Gold Nanoparticle-Based Bioorthogonal Catalysis

  Nano Letters · 2025-06-27 · 4 citations

  articleSenior authorCorresponding

  Bioorthogonal catalysis provides a powerful biomedical tool for controlled 'turn-on' activation of prodrugs and pro-dyes. Gold-based catalysts are highly selective and nontoxic; however, they are susceptible to deactivation by serum proteins and biogenic thiols. We present here a strategy that protects gold nanoparticle (AuNP) catalysts with a lipid corona, enabling bioorthogonal catalysis in biological environments. The modular nature of the lipid corona enables tuning of the surface charge, membrane fluidity, and PEG content. The stability and activity of these lipid-coated AuNPs was demonstrated by successfully converting inactive propargylated doxorubicin to the active drug in cancer cells.

  PublisherDOI

• Light-Triggered Bioorthogonal Nanozyme Hydrogels for Prodrug Activation and Treatment of Bacterial Biofilms

  ACS Applied Materials & Interfaces · 2025-04-24 · 3 citations

  articleSenior authorCorresponding

  Bioorthogonal nanozymes offer in situ activation of pro-dyes and prodrugs using abiotic chemical transformations. Bacterial infections, especially biofilm-associated infections, are extremely difficult to treat due to obstacles such as poor antibiotic penetration and the rising threat of antibiotic resistance. Spatiotemporal control of bioorthogonal catalysis provides a strategy for “on-demand” generation of therapeutics, effectively localizing therapeutic action and minimizing side effects. Here, we present the fabrication of visible-light-responsive alginate hydrogel beads embedded with bioorthogonal polyzymes (PZs). Exposure to a 405 nm light induces the reduction of Fe(III) to Fe(II), triggering the dissolution of the PZ-gel beads with concomitant release and activation of the polyzyme. This approach enabled the selective activation of a prodrug of Linezolid, a last-in-line antibiotic for Gram-positive bacterial infections, enabling the targeted eradication of multidrug-resistantStaphylococcus aureus biofilms. Overall, the use of alginate biomaterial along with noninvasive visible light offers a nontoxic platform for spatiotemporal release of antibiotics through bioorthogonal activation.

  PublisherDOI

Recent grants

• Nanosensor-Based Phenotypic Screening for Precision Therapy of Cancer Stem Cells

  NIH · $300k · 2017–2019

• International Collaboration in Chemistry: Synergistic Tailoring of Flavins and Quantum Dots for Solar Cell Applications

  NSF · $425k · 2010–2014

• Plasmon-Enhanced Chiroptical Biosensors

  NSF · $400k · 2013–2017

• Nanoparticle-Stabilized Capsules as Drug Delivery Systems

  NIH · $408k · 2010–2013

• Intracellular Host-Guest Activation of Nanoparticle Therapeutics

  NIH · $1.0M · 2012–2015

Frequent coauthors

• Graeme Cooke

  University of Glasgow

  129 shared

• Paul S. Weiss

  California NanoSystems Institute

  91 shared

• Scott J. Miller

  NextFlex

  85 shared

• Jonathan V. Sweedler

  University of Illinois Urbana-Champaign

  85 shared

• Hongwei Wu

  85 shared

• Lynne S. Taylor

  Purdue University West Lafayette

  85 shared

• Harry A. Atwater

  California Institute of Technology

  85 shared

• J. Justin Gooding

  UNSW Sydney

  85 shared

Labs

• Rotello Research GroupPI

Education

• Postdoc, Chemistry

  Massachusetts Institute of Technology

  1993

• Ph.D., Chemistry

  Yale University

  1990

• Bachelor of Science, Chemistry

  Illinois Institute of Technology

  1985

Awards & honors

• NSF CAREER
• Cottrell Scholar awards
• Camille Dreyfus Teacher-Scholar
• Sloan Fellowships
• Arthur C. Cope Scholar Award (2023)