Progress in the mechanical properties of nanoparticles for tumor-targeting delivery

Cancer nanomedicines have attracted significant attention in the past several decades, and the physicochemical properties, such as the size, shape, composition, surface charge, hydrophobicity, and mechanical properties, of nanoparticles have been optimized for potent cancer therapy. Since publishing our 2020 tutorial review "Influence of nanomedicine mechanical properties on tumor targeting delivery" in Chemical Society Reviews, substantial advancements have been made in understanding the role of mechanical properties in cancer nanomedicine. Notably, in vivo transport processes that are dependent on the mechanical properties of nanomedicine, including long circulation, tumor accumulation, and deep penetration, have been extensively studied using various nano-drug delivery systems. These studies have demonstrated that leveraging these mechanical properties can significantly enhance the antitumor efficacy of nanomedicine. In this review, we categorize the advancements in the mechanical properties of cancer nanomedicine into three distinct themes: the interactions between nanoparticles with varied mechanical properties and cells (2002 - present), the impact of these properties on in vivo delivery processes (2007 - present), and the strategic use of mechanical properties to boost cancer therapy (2023 - present). We analyze how different mechanical properties of organic, inorganic, hybrid, and biological nanoparticles affect their delivery processes at the macroscopic level, i.e., in tissues, organs and cells. At the microscopic level, their biological and physical interactions with biological barriers, physiological structures, cell membranes, organelles, and other structures reveal the potential mechanism of nanoparticles' mechanical properties in determining their antitumor efficacy. Furthermore, we address the current challenges and future prospects in the mechanical properties of cancer nanomedicine, as well as the clinical translation potential of nanoparticles with diverse mechanical characteristics.