An α-lactalbumin-based anticancer nanocarrier platform was designed for efficient rational design and potent in vivo prediction.

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.

The past several decades have witnessed the explosion of nanomedicine for cancer therapy, where notable research efforts have been made in synthesizing and delivering nano‐carriers (NCs) to specific tumor sites. The effective treatment of cancer with nanomedicine poses the requirements of high solubility, prolonged circulation, low toxicity, strong targeting ability, specific distribution, and high tissue penetration capability of NCs, involving interdisciplinary research and posing challenges to the community. Along with experimental contributions for the development and application of NCs to treat cancer, multiscale modeling and simulation have also made considerable contributions to the understanding of the synthesis, translocation, and delivery of NCs and their payloads. Here, recent advances of modeling and simulation work are selected to elucidate some key concepts, methods, and applications of NCs during synthesis and drug delivery, such as assembly, translocation, targeting, cellular uptake, and penetration in tissue. The advantages and limitations of each method are highlighted, and the future perspectives in this field are also discussed.

Germ-mimetic nanoparticles with extended and packed polymer chains can overcome multiple barriers more efficiently.

As the physicochemical properties of ultrafine bubble systems are governed by their size, it is crucial to determine the size and distribution of such bubble systems. At present, the size or size distribution of nanometer-sized bubbles in suspension is often measured by either dynamic light scattering or the nanoparticle tracking analysis. Both techniques determine the bubble size via the Einstein–Stokes equation based on the theory of the Brownian motion. However, it is not yet clear to which extent the Einstein–Stokes equation is applicable for such ultrafine bubbles. In this work, using atomic molecular dynamics simulation, we evaluate the applicability of the Einstein–Stokes equation for gas nanobubbles with a diameter less than 10 nm, and for a comparative analysis, both vacuum nanobubbles and copper nanoparticles are also considered. The simulation results demonstrate that the diffusion coefficient for rigid nanoparticles in water is found to be highly consistent with the Einstein–Stokes equation, with slight deviation only found for nanoparticle with a radius less than 1 nm. For nanobubbles, including both methane and vacuum nanobubbles, however, large deviation from the Einstein–Stokes equation is found for the bubble radius larger than 3 nm. The deviation is attributed to the deformability of large nanobubbles that leads to a cushioning effect for collision-induced bubble diffusion.