Size-Transformable Nanoparticles for Tumor Drug Delivery: Distinct Roles of Shrinkage, Enlargement, and Reassembly

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Although fixed-size nanoparticles have achieved substantial therapeutic success, a single fixed size may not be optimal for the competing requirements of stability in circulation, tumor accumulation, deep tumor penetration, cellular uptake, and intra-tumoral retention. This review frames this fixed-property limitation as the need to switch structural states in response to successive biological barriers and analyzes original research articles published from 2021 to 2025 on large-to-small transformation, small-to-large transformation and assembly, or multistage assembly-disassembly-reassembly. Rather than treating the stimulus or material as an analytical endpoint, the framework maps each pre-, intermediate-, and post-transition state to its biological site and barrier-specific functions. Direction, intermediate structure, site, sequence, and the temporal characteristics were evaluated together with coupled changes in charge, morphology, stiffness, and surface interactions. Large-to-small transformations generally shift the carrier function from tumor accumulation to penetration or uptake, whereas small-to-large transformations support retention, depot formation, or organelle-localized activity. Multistage systems assign distinct functions to the sequential structural states. However, direct in vivo structural evidence and physiologically relevant kinetic measurements have been limited. Future designs should, therefore, verify that the required structure forms at the intended site and time, and directly connect structural transitions with delivery and therapeutic functions.