Awatef M. Alshehri

Directed cell migration is central to the early stages of breast cancer metastasis, when cancer cells detach from the primary tumor and migrate toward distant sites. Here, we use magnetic fields to manipulate this process and examine directional migration and morphology. Magnetic alginate-chitosan (MAC) beads were embedded within a collagen hydrogel to create force-driven micro-topography, and we compared the migration and morphology of MDA-MB-231 breast cancer cells on these constructs. Using video microscopy, we quantified changes in cell shape, velocity, and migration direction in response to intratissue strain. The magnetically actuated cancer metastasis model (MACMM) provides a controllable platform for regulating the magnitude and direction of applied forces to mimic tumor-stroma forces. Highly invasive MDA-MB-231 cells migrated more slowly near the beads, where strain was minimal. A computational model was developed to map magnetic field gradients and stress-strain profiles within the system. Simulations showed that a field gradient of ~159 T/m induces a compressive stress of ~122.8 Pa at 850 µm, decreasing to ~39.4 Pa at 1500 µm, a 3.11-fold difference that correlates with the transition from rounded to elongated cells. Magnetic actuation enables precise control of ECM deformation, strain, and applied force, facilitating the collagen fibers alignment and providing insight into cancer cell responses.

Albumin, the most abundant plasma protein, has emerged as a promising carrier in drug delivery because of its exceptional biocompatibility, stability, and ligand-binding capacity. This chapter explored the role of albumin-based drug delivery systems and focused on their mechanism, recent innovations, and applications. Albumin can bind endogenous and exogenous molecular facilities for transport and controlled release of therapeutic agents, improve drug bioavailability, and minimize adverse effects. It has a long circulatory half-life facilitated by the neonatal Fc receptor (FcRn). This ensures a prolonged, systematic exposure, which makes it a viable option for targeted and sustained drug release. A chapter delves into a multiple drug-binding mechanism, including covalent and noncovalent interactions, nanoparticle formulation, and nanoparticles. The albumin nanoparticles (ABNPs) are particularly significant in modern therapeutics, controlled drug release, enhanced solubility, and tumor targets through receptor-mediated uptake and enhanced permeability and retention (EPR) effects. Through preparation techniques, like desolvation, emulsification, and high-pressure homogenization (NAB™ technology), they optimized an albumin nanoparticle for the enhancement of therapeutic efficacy. A clinical application of the albumin-based system extended beyond oncology, with notable success in diabetes, neurodegenerative disorders, and infectious diseases. The engineered albumin variant and albumin-drug conjugates expand the versatility of precision medicine. Challenges like stability, manufacturing scalability, and the drug-albumin interactions required continued refinement of albumin’s role in drug delivery.

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer.