Preparation Of Nanodrug Based On Polydopamine And Diselenide And Its Application In Photodynamic Therapy

Photodynamic therapy?PDT?has emerged as a clinically approved non-invasive therapeutic modality for cancer treatment,which kills cells with reactive oxygen species?ROS?generated by the reaction between O₂ and the light-activated photosensitizers?PSs?.Due to non-specificity and poor aqueous solubility,PDT efficacy is limited.The use of nanocarriers plays a crucial role in drug delivery and improving the efficiency of PDT.Therefore,it is necessary to develop multifunctional tumor microenvironment responsive nanocarriers with good biocompatibility.In this work,a multifunctional nano drug delivery system MTPP@PDA-Se based on a diselenide-containing polydopamine was designed and synthesized for PDT.Diselanediylbis?propane-3,1-diyl?bis?2-amino-3-?3,4-dihydroxyphenyl?propanoate??DOPA-Se Se-DOPA?was synthesized firstly.DOPA-Se Se-DOPA molecules are composed of two DOPA structures linked by a linker containing a-Se-Se-group.The structure of DOPA-Se Se-DOPA was confirmed by ¹H NMR and HR-MS.Due to the redox sensitivity of the Se-Se bonds,DOPA-Se Se-DOPA molecules can be oxidized and decomposed into selenic acid in the presence of hydrogen peroxide.Then,polydopamine diselenide?PDA-Se?was synthesized easily from DOPA-Se Se-DOPA by solution oxidation.MTPP@PDA-Se nano drug system was obtained by loading a photosensitizer MTPP with mitochondrial targeting ability into PDA-Se nanoparticles.MTPP@PDA-Se nano system were characterized by TEM,DLS,UV-vis absorption spectrum and fluorescence spectrum.MTPP@PDA-Se nanoparticles showed good stability in physiological media.PDA-Se can effectively encapsulate MTPP and quenche the singlet oxygen.In the presence of hydrogen peroxide?100?M?,the Se-Se bonds were cleaved,so that MTPP@PDA-Se nanoparticles decomposed and released MTPP.The effects of MTPP@PDA-Se nano drug on cells were investigated with fluorescence microscope and flow cytometry.MTPP@PDA-Se nanoparticles were internalized by 4T1 cells quickly.Under the light irradiation of 645-655 nm wavelength,MTPP generated singlet oxygen to depolarize the mitochondrial transmembrane potential,which eventually led to cancer cells apoptosis.MTT assays indicate that PDA-Se has a good biocompatibility,and MTPP@PDA-Se nano drug exhibits enhanced toxicity to cancer cells and low side effects.