In vivo non-invasive optical imaging of temperature-sensitive co-polymeric nanohydrogel

Assessment of hyperthermia in pathological tissue is a promising strategy for earlier diagnosis of malignant tumors. In this study, temperature-sensitive co-polymeric nanohydrogel poly(N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) was successfully synthesized by the precipitation polymerization method. The diameters of nanohydrogels were controlled to be less than 100 nm. Also the lower critical solution temperature (LCST, 40 °C) was manipulated above physiological temperature after integration of near-infrared (NIR) organic dye (heptamethine cyanine dye, HMCD) within its interior cores. NIR laser light (765 nm), together with sensitive charge coupled device (CCD) cameras, were designed to construct an NIR imaging system. The dynamic behaviors of PNIPA-co-AA-HMCD composites in denuded mice with or without local hyperthermia treatment were real-time monitored by an NIR imager. The results showed that the PNIPA-co-AA-HMCD composites accumulated in the leg treated with local heating and diffused much slower than that in the other leg without heating. The results demonstrated that the temperature-responsive PNIPA-co-AA-HMCD composites combining with an NIR imaging system could be an effective temperature mapping technique, which provides a promising prospect for earlier tumor diagnosis and thermally related therapeutic assessment.