Self-Assembly Behavior of Emissive Urea Benzene Derivatives Enables Heat-Induced Accumulation in Tumor Tissue

• Published in: Nano letters Vol. 17; no. 4; pp. 2397 - 2403
• Main Authors: Araki, Takeru, Murayama, Shuhei, Usui, Kazuteru, Shimada, Takashi, Aoki, Ichio, Karasawa, Satoru
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12.04.2017
• Subjects: Aminoquinolines - chemistry; Animals; Benzene Derivatives - chemistry; Ethylene Glycol - chemistry; Fluorescent Dyes - chemistry; Hot Temperature; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Neoplasms - diagnostic imaging; Optical Imaging; Particle Size; Surface Properties; Thermodynamics; Tissue Distribution; Urea - analogs & derivatives; Urea - chemistry; Self-assembly; nanoparticles; LCST; tumor imaging; fluorescence
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.6b05371

In this study we describe the construction of a system composed of thermally responsive molecules that can be induced to accumulate in tumor tissues by heating. EgX molecules consisting of an urea–benzene framework and oligoethylene glycol (OEG) functional groups with an emissive aminoquinoline formed nanoparticles (NPs) ∼10 nm in size at 23 °C with a fluorescence quantum yield of 7–10%. At higher temperatures, additional self-assembly occurred as a result of OEG dehydration, and the NPs grew to over 1000 nm in size; this was accompanied by low critical solution temperature behavior. EgXs accumulated in tumor tissues of mice at a body temperature of around 33–35 °C, an effect that was accelerated by external heating around the tumor to approximately 40 °C as a result of increased particle size and enhanced retention in tissue. These EgX NPs can serve as a tool for in vivo monitoring of tumor progression and response to treatment.