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Abstract The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines. 

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 

Abstract Bio/artificial hybrid nanosystems based on biological matter and synthetic nanoparticles (NPs) remain a holy grail of materials science. Herein, inspired by the well‐defined metal–organic framework (MOF) with diverse chemical diversities, the concept of “armored red blood cells” (armored RBCs) is introduced, which are native RBCs assembled within and protected by a functional exoskeleton of interlinked MOF NPs. Exoskeletons are generated within seconds through MOF NP interlocking based on metal‐phenolic coordination and RBC membrane/NP complexation via hydrogen‐bonding interactions at the cellular interface. Armored RBC formation is shown to be generalizable to many classes of MOF NPs or any NPs that can be coated by MOF. Moreover, it is found that armored RBCs preserve the original properties of RBCs (such as oxygen carrier capability and good ex ovo/in vivo circulation property) and show enhanced resistance against external stressors (like osmotic pressure, detergent, toxic NPs, and freezing conditions). By modifying the physicochemical properties of MOF NPs, armored RBCs provide the capability for blood nitric oxide sensing or multimodal imaging. The synthesis of armored RBCs is straightforward, reliable, and reversible and hence, represent a new class of hybrid biomaterials with a broad range of functionalities.