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Abstract Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as‐yet clinically approved antibody therapeutics have targeted extracellular or membrane‐bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier‐based systems. This review summarizes the progress of carrier‐based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye‐labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area.
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Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies
Abstract While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size‐dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non‐invasive in vivo imaging modalities. This allows for visualization and quantification of the whole‐body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non‐invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state‐of‐the‐art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseDiagnostic Tools > in vivo Nanodiagnostics and ImagingNanotechnology Approaches to Biology > Nanoscale Systems in Biology
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- Award ID(s):
- 1930583
- PAR ID:
- 10360552
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- WIREs Nanomedicine and Nanobiotechnology
- Volume:
- 12
- Issue:
- 5
- ISSN:
- 1939-5116
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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