AuNPs) with a size of 50 nm were more easily internalized into mammalian cells than were AuNPs of other sizes (14, 30, 74, and 100 nm). [3] Jiang et al. demonstrated that gold and silver nanoparticlemediated cellular responses were size dependent. [4] Wang et al. reported that the size of micelles significantly influenced their blood circulation time, tumor accumulation, and tumor penetration. [5] Additionally, nanoparticles exhibited sizedependent antibacterial activity and biofilm penetration properties. [6] Typically, small NSs possess the advantages of: 1) high surface-to-volume ratio that provides them with a large surface by which to contact the biological environment, [6b] 2) excellent biosafety and biocompatibility owing to their ease of excretion from living systems, [7] 3) capability to cross intracellular or in vivo barriers such as cell nuclear membranes [8] and blood-brain barriers (BBBs) [9] that allows them to enter these difficult-to-reach regions, and 4) strong penetration ability to reach the depths of solid tumors [10] and bacterial biofilms. [11] In comparison, large NSs typically exhibit long tissue retention periods [12] and slow exocytosis rates from the cells, [13] both of which are ideal for long-term imaging and effective treatment. Moreover, certain large NSs possess more favorable properties than do small ones in regard to enhanced theranostics. [14] To achieve satisfactory theranostic performance in addition to acceptable biosafety, NSs should exhibit the merits of both small and large NSs, and these merits include long-term retention, deep penetration, and rapid clearance. Among the various strategies used for overcoming the size paradox, utilizing size-transformable NSs has been demonstrated to be an available and effective method, as these types of NSs can easily integrate the advantages of small and large NSs. They can behave as small NSs for tissue penetration, rapid clearance, and crossing biological barriers, and can act as large NSs to meet the demands of long-term retention at the targeted sites. During or after the size transformation in these NSs, the loaded drugs within the NSs can be exposed or released from the system, ultimately enabling the transformable NSs to provide a versatile platform for disease theranostics. Based on their superior properties, a great deal of progress in regard to the design and applications of size-transformable NSs has occurred over the last several decades. [15] In this review, we focus on summarizing the design methods and biomedical applications of two types of size-transformable NSs, specifically the size-decreasing and size-increasing NSs. In addition to the The size of nanostructures (NSs) strongly affects their chemical and physical properties and further impacts their actions in biological systems. Both small and large NSs possess respective advantages for disease theranostics, and this therefore presents a paradox when choosing NSs with suitable sizes. To overcome this challenge, size-transformable NSs have emerged as a powerful tool,...
