Here, we demonstrate that a simple nanoparticle can be used as a contrast agent for biomedical imaging in six different modalities. Near infrared (NIR) fluorescence (FL), NIR-to-NIR upconversion (UC) luminescence, photoacoustic (PA) imaging, Cerenkov luminescence (CL), X-ray computed tomography (CT) and positron emission tomography (PET) were compared in phantom studies and then used for lymphatic mapping in mice. The nanoparticle is self-assembled from just two active imaging components: porphyrin-phospholipid, which coats a core-shell upconversion nanosphere. The porphyrin-phospholipid provides strong absorption for PA, allows for self-assembly-responsive FL, and enables seamless post-labeling with 64Cu for PET and CL. The core-shell provides UC that is not quenched by the porphyrin coating as well as electron density for CT.

Advances in biomedical imaging have spurred the development of integrated multimodal scanners, usually capable of two simultaneous imaging modes. The long-term vision of higher-order multimodality is to improve diagnostics or guidance through analysis of complementary, data-rich, co-registered images. Synergies achieved through combined modalities could enable researchers to better track diverse physiological and structural events, analyze biodistribution and treatment efficacy, and compare established and emerging modalities. Higher-order multimodal approaches stand to benefit from molecular imaging probes and in recent years, contrast agents that have hypermodal characteristics have increasingly been reported in preclinical studies. Given the chemical requirements for contrast agents representing various modalities to be integrated into a single entity, higher-order multimodal agents reported so far tend to be of nanoparticulate form. To date, the majority of reported nanoparticles have included components that are active for magnetic resonance. Herein, we review recent progress in higher-order multimodal imaging agents, which span a range of material and structural classes, that have demonstrated utility in three (or more) imaging modalities.

Biomedical applications of porphyrins and related molecules have been extensively pursued in the context of photodynamic therapy. Recent advances in nanoscale engineering have opened the door for new ways that porphyrins stand to potentially benefit human health. Metalloporphyrins are inherently suitable for many types of medical imaging and therapy. Traditional nanocarriers such as liposomes, dendrimers and silica nanoparticles have been explored for photosensitizer delivery. Concurrently, entirely new classes of porphyrin nanostructures are being developed, such as smart materials that are activated by specific biochemicals encountered at disease sites. Techniques have been developed that improve treatments by combining biomaterials with photosensitizers and functional moieties such as peptides, DNA and antibodies. Compared to simpler structures, these more complex and functional designs can potentially decrease side effects and lead to safer and more efficient phototherapies. This review examines recent research on porphyrin-derived materials in multimodal imaging, drug delivery, bio-sensing, phototherapy and probe design, demonstrating their bright future for biomedical applications.

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