Scientists Dress Living Bacteria in Mussel-Inspired Coatings to Fight Colitis and Cancer

Scientists at Shanghai Jiao Tong University have unveiled a detailed protocol that could reshape how living cells are engineered for medicine. Writing in Nature Protocols, Lu Wang and Jinyao Liu describe a flexible chemical strategy that coats the surfaces of living bacteria using in situ dopamine polymerization, allowing researchers to attach custom functional molecules directly onto cells without touching their genomes. The approach, inspired by the adhesive chemistry marine mussels use to cling to rocks, sidesteps many of the limitations that have constrained genetic cell engineering and opens a path toward designer cellular therapeutics assembled in a matter of hours.

Cell engineering has become one of the most promising frontiers in biomedicine, underpinning therapies ranging from CAR-T cancer treatments to engineered probiotics. Yet the dominant tool for endowing cells with new abilities—genetic manipulation—carries inherent constraints. Editing multiple genes simultaneously is technically complex, and the tools that work in one species often fail to translate to another. As a result, building cells with sophisticated, multi-part functionalities through genetic means remains slow, costly and sometimes infeasible.

The cell surface offers a compelling alternative target. Because it mediates virtually every interaction a cell has with its environment, the surface is where therapeutic behavior can be most directly tuned. Surface biomolecules present a rich array of functional groups—amines, thiols and other reactive chemistry—that serve as natural anchoring points for chemical modification. Wang and Liu exploited this chemical accessibility by harnessing dopamine, a small molecule that self-polymerizes under mild, alkaline conditions into polydopamine, a adhesive layer first described in a landmark 2007 Science paper on mussel-inspired surface chemistry.

The beauty of the method lies in its simplicity and universality. When dopamine is added to a suspension of living bacteria under the right conditions, it polymerizes directly on the cell surface, forming a thin reactive coating that can simultaneously capture a second component of choice. In the protocol’s first procedure, that component is polyethylene glycol, or PEG, a hydrophilic polymer long known to help nanoparticles slip through mucus. The result is a PEGylated bacterium capable of penetrating the intestinal mucus layer and reinforcing the mucosal barrier—a potential preventive strategy against colitis. Excluding bacterial culture, preparing these mucus-penetrating bacteria takes roughly three hours.

The second procedure goes a step further with dual-functionalization. Here, polydopamine serves as the bridge between two distinct bioactive molecules on a single bacterium: an anti-PD1 antibody, a celebrated immune checkpoint inhibitor, and the S1 subunit of the SARS-CoV-2 spike protein, a viral antigen. The resulting synergy-immunoactivation bacteria are designed to simultaneously provoke anticancer immunity and antiviral immunity, offering a two-in-one platform for treating tumors while guarding against infection. This dual-functionalization procedure requires only about one hour of hands-on preparation time beyond bacterial culture.

Compared with conventional genetic manipulation and existing physicochemical surface modification techniques, the protocol’s versatility stands out. The polydopamine intermediate accepts both natural biological macromolecules, such as proteins and antibodies, and synthetic materials, and it tolerates the attachment of multiple diverse components in sequence. Because the chemistry does not depend on species-specific genetic machinery, it can in principle be applied to a wide range of cell types, from probiotic Escherichia coli Nissle 1917 to potentially other living cells, making it a genuinely cross-species platform.

The scientific foundations of the work draw on more than a decade of polydopamine research. Catecholic chemistry, first systematized for surface modification by Messersmith, Lee and colleagues, has been applied to countless materials, but extending it to living cells required careful optimization to ensure the polymerization conditions do not compromise cell viability. The Wang and Liu groups had previously demonstrated polymerization-mediated multifunctionalization of living cells in Advanced Materials in 2021, and their primary research papers—published in Nature Biomedical Engineering in 2024 on mucus-penetrating PEGylated bacteria and in Advanced Materials in 2023 on hybrid immunoactive nanosurface bacteria—provide the proof-of-concept data that underpin this protocol.

The therapeutic implications are substantial. For inflammatory bowel disease, the mucus-penetrating bacteria represent a novel way to shore up a failing intestinal barrier rather than simply delivering drugs. For oncology, bacteria coated with checkpoint inhibitors concentrate immunotherapy at tumor sites, potentially reducing the systemic toxicity associated with injected antibodies while leveraging the natural tumor-homing behavior of certain bacterial strains. And because the coating chemistry is modular, the same scaffold could in principle carry different antigen–antibody pairs to address other cancers or emerging viral threats.

The authors also confront the practical challenges facing any live biotherapeutic. Regulatory frameworks for live biotherapeutic products, as outlined by the US Food and Drug Administration, demand rigorous characterization of manufacturing and control, and a surface-engineered bacterium must demonstrate stability, safety and reproducibility at every step. The protocol addresses these concerns by providing detailed characterization procedures, including assessments of coating thickness, surface composition, bacterial viability, mucus penetration, and the immunogenicity and intratumoral distribution of the dual-functionalized bacteria. Jinyao Liu has additionally filed a patent related to the technology, signaling commercial interest alongside the academic contribution.

By transforming cell surface engineering from a specialized genetic exercise into an accessible chemical operation, the protocol lowers the barrier to entry for laboratories seeking to develop next-generation living therapeutics. The authors anticipate that the platform will offer valuable guidance for engineering living cells with designable, tailorable functionalities for innovative cell-based therapy. If the approach translates from the bench to the clinic as hoped, the humble chemistry of mussel glue may soon help dress living cells for battle against some of medicine’s most stubborn diseases.

Subject of Research: Dopamine polymerization-mediated chemical surface functionalization of living cells for cell-based therapy

Article Title: Dopamine polymerization-mediated surface functionalization of living cells for advanced therapeutic applications

Article References: Dopamine polymerization-mediated surface functionalization of living cells for advanced therapeutic applications. (n.d.). https://doi.org/10.1038/s41596-026-01422-1

Image Credits: AI Generated

DOI: 10.1038/s41596-026-01422-1

Keywords: dopamine polymerization, polydopamine, surface functionalization, living cells, bacterial therapeutics, mucus-penetrating bacteria, PEGylation, immune checkpoint inhibitor, anticancer immunity, antiviral immunity, cell engineering, colitis