With potential applications in materials and especially in light-responsive biomedicine that targets cancer tissue selectively, much research has focused on developing covalent conjugation techniques to tether porphyrinoid units to various biomacromolecules. This review details the key synthetic approaches that have been employed in the recent decades to conjugate porphyrinoids with oligonucleotides and peptides/proteins. In addition, we provide succinct discussions on the subsequent applications of such hybrid systems and also give a brief overview of the rapidly progressing field of porphyrin-antibody conjugates. Since nucleic acid and peptide systems vary in structure, connectivity, functional group availability and placement, as well as stability and solubility, tailored synthetic approaches are needed for conjugating to each of these biomacromolecule types. In terms of tethering to ONs, porphyrins are typically attached by employing bioorthogonal chemistry (e.g., using phosphoramidites) that drive solid-phase ON synthesis or by conducting post-synthesis modifications and subsequent reactions (such as amide couplings, hydrazide-carbonyl reactions, and click chemistry). In contrast, peptides and proteins are typically conjugated to porphyrinoids using their native functional groups, especially the thiol and amine side chains. However, bioorthogonal reactions (e.g., Staudinger ligations, and copper or strain promoted alkyne-azide cycloadditions) that utilize de novo introduced functional groups onto peptides/proteins have seen vigorous development, especially for site-specific peptide-porphyrin tethering. While the ON-porphyrin conjugates have largely been explored for programmed nanostructure self-assembly and artificial light-harvesting applications, there are some reports of ON-porphyrin systems targeting clinically translational applications (e.g., antimicrobial biomaterials and site-specific nucleic acid cleavage). Conjugates of porphyrins with proteinaceous moieties, on the other hand, have been predominantly used for therapeutic and diagnostic applications (especially in photodynamic therapy, photodynamic antimicrobial chemotherapy, and photothermal therapy). The advancement of the field of porphyrinoid-bioconjugation chemistry from basic academic research to more clinically targeted applications require continuous fine-tuning in terms of synthetic strategies and hence there will continue to be much exciting work on porphyrinoid-biomacromolecule conjugation.
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Engineered protein–iron oxide hybrid biomaterial for MRI-traceable drug encapsulation
Labeled protein-based biomaterials have become popular for various biomedical applications such as tissue-engineered, therapeutic, and diagnostic scaffolds. Labeling of protein biomaterials, including with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging and therapeutic techniques. These USPIO-based biomaterials are widely studied in magnetic resonance imaging (MRI), thermotherapy, and magnetically-driven drug delivery, which provide a method for direct and non-invasive monitoring of implants or drug delivery agents. Where most developments have been made using polymers or collagen hydrogels, shown here is the use of a rationally designed protein as the building block for a meso-scale fiber. While USPIOs have been chemically conjugated to antibodies, glycoproteins, and tissue-engineered scaffolds for targeting or improved biocompatibility and stability, these constructs have predominantly served as diagnostic agents and often involve harsh conditions for USPIO synthesis. Here, we present an engineered protein–iron oxide hybrid material comprised of an azide-functionalized coiled-coil protein with small molecule binding capacity conjugated via bioorthogonal azide–alkyne cycloaddition to an alkyne-bearing iron oxide templating peptide, CMms6, for USPIO biomineralization under mild conditions. The coiled-coil protein, dubbed Q, has been previously shown to form nanofibers and, upon small molecule binding, further assembles into mesofibers via encapsulation and aggregation. The resulting hybrid material is capable of doxorubicin encapsulation as well as sensitive -weighted MRI darkening for strong imaging capability that is uniquely derived from a coiled-coil protein.
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- Award ID(s):
- 1728858
- NSF-PAR ID:
- 10374254
- Date Published:
- Journal Name:
- Molecular Systems Design & Engineering
- Volume:
- 7
- Issue:
- 8
- ISSN:
- 2058-9689
- Page Range / eLocation ID:
- 915 to 932
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d2me00002d
