Smart self-transforming nano-systems for overcoming biological barrier and enhancing tumor treatment efficacy.

Nanomedicines need to overcome multiple biological barriers in the body to reach the target area. However, traditional nanomedicines with constant physicochemical properties are not sufficient to meet the diverse and sometimes conflicting requirements during in vivo transport, making it difficult to penetrate various biological barriers, resulting in suboptimal drug delivery efficiency. Smart self-transforming nano-systems (SSTNs), capable of altering their own physicochemical properties (including size, charge, hydrophobicity, stiffness, morphology, etc.) under different physiological conditions, hold the potential to break through multiple biological barriers, thereby improving drug delivery efficiency and the efficacy of cancer treatment. In this review, we first summarize the design strategies of five most popular SSTNs (such as size-, charge-, hydrophilicity-, stiffness-, and morphology-self-transforming nano-systems), and then delve into their biomedical applications in enhancing circulation time, tissue penetration, and cellular uptake. Finally, we discuss the opportunities and challenges that SSTNs face in the future for cancer treatment and diagnosis.