Size-Dependent Penetration of Nanoparticles in Tumor Spheroids: A Multidimensional and Quantitative Study of Transcellular and Paracellular Pathways.

Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA-MB-231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi-spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA-MB-231 cells and spheroids with or without an energy-dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two-photon microscopy, and synchrotron X-ray fluorescence microscopy. The results reveal that 15 nm nanoparticles penetrate spheroids mainly through an energy-independent transcellular pathway, while 60 nm nanoparticles penetrate primarily through an energy-dependent transcellular pathway. Meanwhile, 22 nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site.

Self-Propelled Initiative Collision at Microelectrodes with Vertically Mobile Micromotors.

Impact experiments enable single particle analysis for many applications. However, the effect of the trajectory of a particle to an electrode on impact signals still requires further exploration. Here, we investigate the particle impact measurements versus motion using micromotors with controllable vertical motion. With biocatalytic cascade reactions, the micromotor system utilizes buoyancy as the driving force, thus enabling more regulated interactions with the electrode. With the aid of numerical simulations, the dynamic interactions between the electrode and micromotors are categorized into four representative patterns: approaching, departing, approaching-and-departing, and departing-and-reapproaching, which correspond well with the experimentally observed impact signals. This study offers a possibility of exploring the dynamic interactions between the electrode and particles, shedding light on the design of new electrochemical sensors.