In Vivo Imaging And Cancer Therapy Of The PEG-IR-780-C13 Micelle And The Cardiotoxicity Study Of Doxorubicin-albumin Nanoparticles

IR-780, a representative hydrophobic near-infrared (NIR) fluorescence dye, is cable of fluorescently imaging and photothermal therapy in vitro and in vivo. However, insolubility in all pharmaceutically acceptable solvents limits its further biological applications. To increase solubility, we developed a novel self-assembled IR-780 containing micelle (PEG-IR-780-C13) based on the structural modification of IR-780. In addition, PEG-IR-780-C13 micelles are specifically targeted to the tumor after intravenous injection and can be used for tumor imaging. The in vivo photothermal therapy experiments indicate that CT-26 xenograft tumors can be effectively ablated by combining PEG-IR-780-C13 micelles with 808nm laser irradiation. More importantly, no significant toxicity can be observed after intravenous administration of the therapeutic dose of generated micelles. Overall, our micelles may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.Doxorubicin is an antitumor drug commonly used against a wide spectrum of tumors. However, the clinical application of doxorubicin is restricted by its cardiotoxicity. To reduce the cardiotoxicity, we develop an albumin based nanocarrier via a new molecular switch method for DOX delivery. Spherically shaped NPs-DOX (doxorubicin loaded albumin nanoparticles) are prepared with a drug loading capacity and particle size of 4.3% and 120.1±26 nm, respectively.In vitro the uptake of NPs-DOX and efficacy experiments show that NPs-DOX can be made more efficient uptake by cells and retains its cytotoxicity. In vivo studies demonstrate that NPs-DOX is able to preferentially accumulate in tumor and show great tumor inhibition on H22 hepatocellular carcinoma bearing mice. As for the toxicity, compared with free DOX, the maximum tolerated dose of NPs-DOX is increased from 10mg/kg to over 30 mg/kg, indicating the reduced systematic toxicity. More importantly, the cardiotoxicity induced by NPs-DOX is also significantly reduced since both LVEF (left ventricular ejection fraction) and LVFS (left ventricular fractional shortening) are almost not changed and other cardiotoxicity markers such as CK-MB (serum creatine kinase-MB), LDH(lactate dehydrogenase), SOD (superoxide dismutase) and MDA (malonaldehyde) are kept constant. The reduced cardiotoxicity of NPs-DOX is also confirmed by none histological changes in the heart tissue, which is verified by pathological tissue sections. Therefore, such albumin based nanocarrier can be a promising strategies for the delivery of doxorubicin.