Understanding the In Vivo Fate of Advanced Materials by Imaging

Abstract

Engineered materials are ubiquitous in biomedical applications ranging from systemic drug delivery systems to orthopedic implants, and their actions unfold across multiple time‐ and length‐scales. The efficacy and safety of biologics, nanomaterials, and macroscopic implants are all dictated by the same general principles of pharmacology as applied to small molecule drugs, comprising how the body affects materials (pharmacokinetics, PK) and conversely how materials affect the body (pharmacodynamics, PD). Imaging technologies play an increasingly insightful role in monitoring both of these processes, often simultaneously: translational macroscopic imaging modalities such as magnetic resonance imaging and positron emission tomography/computed tomography offer whole‐body quantitation of biodistribution and structural or molecular response, while ex vivo approaches and optical imaging via in vivo (intravital) microscopy reveal behaviors at subcellular resolution. In this review, the authors survey developments in imaging the in situ behavior of systemically and locally administered materials, with a particular focus on using microscopy to understand transport, target engagement, and downstream host responses at a single‐cell level. The themes of microenvironmental influence, controlled drug release, on‐target molecular action, and immune response, especially as mediated by macrophages and other myeloid cells, are examined. Finally, the future directions of how new imaging technologies may propel efficient clinical translation of next‐generation therapeutics and medical devices are proposed.

Strategies for Delivering Nanoparticles across Tumor Blood Vessels

“…[ 197 ] Light sheet fluorescence microscopy can then be used for fast, high resolution, optically sectioned imaging, followed by computational 3D reconstruction. [ 198 ] These concepts are covered in great detail in a recently published review by Weissleder and co‐workers [ 199 ] Tissue clearing and light sheet microscopy have been combined with machine learning algorithms to create a framework for quantifying and analyzing brain vasculature, called the vessel segmentation and analysis pipeline (VesSAP), for automatic, unbiased, and scalable vasculature analysis. [ 200 ] The use of optical and electron microscopy methods could provide answers to the questions that surround the complex mechanisms behind nanoparticle accumulation in solid tumors.…”

X‐Ray Visible Protein Scaffolds by Bulk Iodination

“…To do this we have exploited an obsolete radiochemistry method, adapting it for the first time to produce radiopaque biomaterials by combining stable iodine isotopes and macroscopic protein scaffolds. This builds on the growing interest in labeling biological and biodegradable polymers for non-invasive imaging, [25] including incorporation of radionuclides for nuclear imaging, [66][67][68] contrast agents for MRI, [69][70][71][72][73] as well as high-Z elements for CT imaging. [27,71,[74][75][76][77] Compared to radionuclide-based polymer labeling methods, [56,58] CT imaging offers greater resolution, while overcoming the limitations associated with label half-life, thus enabling imaging at significantly later time points post-transplantation.…”

“…[5,19] Yet in order for emerging biomaterial therapies to reach maturity, it is crucial to validate their behavior and safety post-implantation. [23][24][25] However, this task remains challenging due to the inherent resemblance between protein-based implants and native tissue, with both generating similar signals on commonly used medical imaging modalities such as Magnetic Resonance Imaging (MRI), X-ray Computed Tomography (CT), and ultrasound. Consequently, detection of critical events such as successful delivery and integration, mis-delivery, mechanical failure, or detachment proves unachievable in both preclinical models and patient populations, primarily due to the limited availability of imageable scaffolds.…”

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“…Drug discovery is a time-consuming and high-cost process, and the accurate monitoring of drug distribution and efficacy, both in vitro and in vivo, thus plays a vital role in reliable identification and optimization of drug candidates [ 1 , 2 ]. Molecular bioimaging provides new opportunities to study drug transport in biological systems with spatial and temporal resolutions by integration with advanced techniques, such as positron emission tomography (PET) and computed tomography (CT) [ 3 , 4 ]. Amongst the various monitoring methods, fluorescence-based approaches are quite promising owing to their non-invasiveness, real-time detection, high resolution, qualitative/quantitative capability, and can be employed in various biological systems, e.g., animal models, tissue-based samples and single cells.…”