Study Of Magnetic Nanoparticles With Redox Response For Photodynamic Antitumor

In recent years,photodynamic therapy?PDT?has been increasingly used in anti-tumor research because of its good non-invasiveness,non-multidrug resistance,and precise treatment.However,tumor hypoxia largely limits the therapeutic effect of PDT.In addition,PDT mainly uses its reactive oxygen species?ROS?to kill tumor cells,but ROS has a short half-life and diffusion radius,making it is difficult to effectively damage macromolecules and organelles in tumor cells,thus the therapeutic effect of PDT which is also affected.Therefore,increasing the oxygen concentration in the tumor site and generating ROS in situ at the ROS-sensitive position of the tumor cells to improve the anti-tumor effect of PDT is promising strategy for tumor treatment.In this paper,we designed an anti-tumor nanoplatform that increased the oxygen concentration at the tumor site and targeted the mitochondria of tumor cells.We firstly prepared a triphenylphosphine modified dextran?Dex-TPP?coated magnetic ferroferric oxide nanoparticle Fe₃O₄@Dex-TPP?FDT NPs?by coprecipitation method.The surface of FDT NPs is grafted with the photosensitizer protoporphyrin?PpIX?and the disulfide-containing polyethylene glycol monomethyl ether?mPEG-ss-COOH?to obtain the final magnetic nanoparticle Fe₃O₄@Dex-TPP/PpIX/ss-mPEG?FDTPSP NPs?.In the synthetic process,we detected the structure and properties of all the materials by nuclear magnetic resonance spectroscopy?¹H NMR?,infrared spectroscopy?FT-IR?,ultraviolet-visible absorption spectroscopy?UV-vis?,dynamic light scattering nanoparticle size analyzer?DLS?,thermogravimetric analysis?TGA?,transmission electron microscopy?TEM?,atomic force microscopy?AFM?,X-ray diffraction analysis?XRD?and vibration sample magnetometer?VSM?.The results showed that the magnetic nanoparticles were successfully prepared with small size?about 70 nm?.And the nanoparticles can expose positively charged TPP in response to glutathione?GSH?,resulting in the Zeta potential of nanoparticles increased from-6mV to+13 mV,which is benefit for mitochondria targeting.Fe₃O₄ can be decomposed into Fe²⁺/Fe³⁺in a slightly acidic environment,which can catalyze the decomposition of H₂O₂ to produce oxygen?O₂?and hydroxyl radical?·OH?through Fenton reaction,further to enhance the PDT effect.Subsequently,the cytocompatibility and anti-tumor effect of the nanoparticles were investigated by flow cytometry?FCM?,fluorescence microscopy?FM?,magnetic resonance imaging?MRI?and other instruments.It can be seen that the nanoparticles successfully enter the cytoplasm through photoinduced internalization?PCI?,and subsequently interact with GSH in tumor cells to expose TPP,finally targets and damages the mitochondria of tumor cells,leading to the apoptosis of tumor cells.Furthermore,the nanoparticles have MR imaging effects.Finally,tumor models were established in the breast of Balb/c mice with 4T1 cells,and the in vivo antitumor effects of the nanoparticles were examined by these tumor-bearing mice.The changes of body weight and tumor volume of the mice were recorded and analyzed.Then,the tissue section of the tumor and main organs of the mice were analyzed by hematoxylin-eosin?H&E?staining,terminal deoxy nucleotidyl transferase mediated UTP end labeling?TUNEL?and Ki67 staining.The results showed that FDTPSP NPs with illumination group had the best in vivo anti-tumor effect.