Precise Control of Shape-Variable Nanomicelles in Nanofibers Reveals the Enhancement Mechanism of Passive Delivery

Nowadays, the development of nanoparticles is known to be mainly associated with enhancement of the targeted delivery of the active component to solid tumors. However, the lack of understanding of the nanoparticle morphology restricts the transport efficiency of various nanocarriers, especially offers no consistent mechanism for the delivery. Here, we demonstrate the principles of enhancement of passive delivery utilizing the precise control and analysis of shape-switchable nanomicelles without any functional addition. We successfully regulated the nanomicelle shape with various aspect ratios in the electrospun nanofiber matrix and devised a stretching phase diagram. Using the vascular leakage model, visual laser spectrum, and image analysis in the simulated scene, we found that the deformed nanomicelles with high aspect ratios along with lower equivalent volumes were significantly beneficial to the passive delivery. Further, the enhanced permeability of the shape-variable nanomicelles in the recovering state was up to 4 times of that observed before recovery. Our results challenge the current consensus of passive targeting and provide an important guidance for the design of nanoparticle morphology and active addition in cancer nanomedicine.