Polymeric Contrast Agents for In Vivo Imaging: From Molecular Design to Multimodal Translation

Diagnostic imaging has traditionally relied on small-molecule and inorganic contrast agents—iodinated compounds, gadolinium chelates, organic dyes, and radiotracers—whose performance is limited by rapid renal clearance, narrow circulation windows, modest targeting specificity, and, in several cases, persistent safety concerns. These shortcomings are rooted not primarily in imaging chemistry, but in materials design. The parameters that determine whether a contrast agent reaches its target, remains there to generate sufficient signal, and clears safely are governed by molecular architecture, surface chemistry, size, and degradability. This perspective places macromolecular and soft-matter design at the core of next-generation contrast agent development. Yet despite intensive effort across individual imaging modalities, the design rules linking polymeric architecture to in vivo fate remain dispersed across polymer, imaging, and translational research communities, seldom articulated as a unified scientific challenge.

This Research Topic explicitly frames contrast enhancement as a problem of polymer design. Polymeric platforms—block copolymers, dendrimers, hyperbranched and bottlebrush architectures, nanogels, micelles, and self-assembled colloids—offer synthetically tunable control over the structural parameters that define biological behavior. Architectural features and molecular weight dictate the balance between renal and hepatobiliary clearance; surface chemistry and stealth coatings (PEG and emerging alternatives) affect circulation and corona formation; backbone composition controls biodegradability and fate of degradation products; and the entire construct must meet strict standards of safety, low immunogenicity, and scalable manufacture. We particularly invite studies that treat these design–fate–safety relationships as the scientific core, rather than as secondary considerations. Across all imaging modalities, we prioritize work in which polymer architecture, surface chemistry, or backbone behavior directly determines imaging performance, as opposed to cases where polymers act merely as inert carriers.

To gather further insights into polymer design as a determinant of imaging performance and translational success, we welcome contributions addressing, but not limited to, the following themes:

- Macromolecular architecture and its influence on biodistribution, circulation, and renal versus hepatobiliary clearance

- Surface engineering, stealth chemistries, and protein-corona effects on imaging outcomes

- Polymeric MRI agents, including macromolecular Gd and Mn conjugates, 19F probes, CEST-active polymers, and polymer-stabilized iron oxide systems

- NIR-II fluorescence and optical contrast optimized through polymer engineering of dye microenvironments, aggregation, and photostability

- Radiolabeled and chelator-functionalized polymers for PET and SPECT (e.g., ⁶⁴Cu, ⁸⁹Zr, ⁶⁸Ga)

- Semiconducting polymer nanoparticles and absorber-loaded architectures for photoacoustic imaging

- Multimodal and theranostic constructs integrating polymer scaffolds with therapeutic functions (photoactive, drug, or genetic payloads)

- Stimuli-responsive and activatable polymer systems modulating signal in response to pH, redox, enzyme activity, or temperature

- Biocompatibility, immunogenicity, degradation, and regulatory/translational pathways for clinical advancement

- Scalable synthesis and reproducible manufacture of imaging-grade polymeric materials

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Methods
• Mini Review
• Original Research
• Perspective
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Methods
• Mini Review
• Original Research
• Perspective
• Review

Keywords: Polymeric contrast agents, macromolecular imaging probes, stimuli‑responsive polymers, multimodal theranostics, NIR‑II fluorescence imaging, polymer architecture and biodistribution, biodegradable imaging materials

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.