Next-Generation Transformable Nanomedicines: Revolutionizing Cancer Drug Delivery and Theranostics

Nanomedicine has significantly advanced the treatment of various cancer phenotypes, addressing numerous challenges associated with conventional therapies. Researchers have extensively investigated the physicochemical properties of nanocarriers, such as charge, morphology, and surface chemistry, to optimize drug delivery systems. In the context of transformable nanomedicine, these properties are particularly critical for overcoming existing limitations, including suboptimal blood circulation times, sequestration by the reticuloendothelial system and mononuclear phagocyte system, and inefficient targeting of the tumor microenvironment (TME). Alterations in nanocarrier geometry, surface charge, and hydrophilicity have shown potential in mitigating these barriers, offering improved therapeutic outcomes and enhanced biomedical applications. This review explores controlled modulation of these properties in the context of anticancer therapy, offering an in-depth exploration of transformable strategies activated by both internal and external stimuli. We analyze the implications of these tunable characteristics on pharmacokinetics, biodistribution, and targeted delivery to the TME. Additionally, we address the current challenges in the clinical translation of these advanced nanocarriers and propose strategies to overcome these obstacles to enhance the clinical feasibility of nanomedicine-based cancer therapies.