Rubber-band-like polymeric nanotoroids’ preparation and their agile effects in anticancer drug delivery

In this study, an agile anticancer drug-conjugatable toroidal mixed micelle (TMM) platform was developed. When observed under a high-speed real-time microscope, the drug-loaded TMMs exhibited dynamic transformation, displaying rubber-band-like characteristics under both static and flow conditions. Microscopic observations revealed that the spherical mixed micelles (SMMs) were internalized by cells upon their attachment in a static state or under flow conditions, whereas the TMMs were taken up by the cells only when coming into contact with expanding surfaces during their dynamic transformation. This effect resulted in a reduction in the total cellular uptake of TMMs by macrophage cells. In addition, the agile effect of TMMs affords them an exceptional ability to penetrate tumor spheroids in a static state and imparts exceptional extrusive ability when they flow through small pores. The in vivo studies conducted in this work demonstrate their superior ability to penetrate ruptured blood vessels, accumulate in tumor lesions, and avoid macrophage uptake into the liver or spleen. These in vivo studies also indicate that the TMMs eliminated cancerous cells deep within tumors while causing no injury to the liver and spleen, while SMMs displayed suboptimal tumor inhibition, due to their deposits in the proximity of blood vessels. Our TMM platform is feasible as a drug delivery system in anticancer applications. • In this study, a new chemical modality to fabricate the polymeric nanotoroids via undergoing the sphere-to-toroid transition was exploited. During the transition, the in situ reactive sites were produced for the drug conjugation. • This is the first study to disclose the rubber-band-like dynamic transformation and the agile contact orientation effect of the polymeric nanotoroids. This is also the first report to shed light on the relevance of these behaviors and biological effects as drug delivery system in anticancer therapy. • In comparison with the spherical counterparts, toroidal mixed micelles manifested superior in vitro extrusive ability from the small pores and tumor spheroid penetration, with little enclosure into macrophages under flows. Subsequently, the in vivo results attested that more toroidal mixed micelles enabled to convey from ruptured blood vessels and accumulate into tumors in major. After a long-term treatment, the toroidal mixed micelles resulted in massive cells apoptosis within tumor lesions, while they caused fewer injuries to macrophage-enriched organs, such as liver and spleen.