Hydrophobic IR780 Encapsulated In Biodegradable Human Serum Albumin Nanoparticles For Photothermal And Photodynamic Therapy

Near infrared dyes (NIR dyes) are small organic molecules with the wavelength range from 700-1000 nm, which can be taken as Photosensitizers. After absorbing NIR light with specific wavelengths, part of the energy Photosensitizers obtained will release as long-wavelength fluorescences which can be applied for tumor imaging. While the rest of the energy will turn into amount of heat and can transform oxygen from the surroundings into Reactive Oxygen Species (ROS), resulting in the death of tumor cells. Therefore, Photosensitizers can also be used for photothermal and photodynamic combination therapy for tumors.IR780, a near-infrared dye, can preferentially accumulate in tumor cells via relatively high tumor mass membrane potential and organic anion transporter peptides (OATPs). So far, it has been reported that IR780 can be applied for cancer imaging, photodynamic therapy (PDT) and photothermal therapy (PTT). However, due to the existing lipophilic group, free IR780 is extremely difficult to be dissolved in water that severely limits it further application in clinic. And free IR780 is unstable in aqueous solution and sensitive to natural light. Moreover, the toxicity of free IR780 is also a concern due to it has low maximal tolerance dose in present reports. Although many researchers have done a lot work to overcome these disadvantages by encapsulating IR780 into various nanomaterials(e.g. Re-labeled polymeric micelles, silica nanoparticles, and heparin-folic acid nanoparticles), they still couldn’t solve the problem of the poor tolerance of IR780, and might cause the damage to the organs in the body. Therefore, it is necessary to develop a simple method for delivering IR780, which not only increases the water solubility and stability but also reduces the toxicity of IR780.In this study, human serum albumin was used to load IR780 to form nanoparticles (HSA-IR780 NPs) by protein self-assembly. Compared to free IR780, the solubility of HSA-IR780 NPs was greatly increased (1,000 folds) while the toxicity was decreased (from 2.5 mg/kg to 25 mg/kg). Moreover, both PTT and PDT could be observed in HSA-IR780 NPs as determined by increased temperature and enhanced generation of singlet oxygen after laser irradiation at 808 nm. In vivo studies also showed a great tumor inhibition by injection of HSA-IR780 NPs into tumor-bearing mice.Therefore, HSA-IR780 NPs may serve as a promising substitute for IR780 in further clinical PDT and PTT for tumors.