Study On The Preparation Of Photodynamic-based Nanoplatform And Application In Tumor Treatment

The recurrence of tumor becomes major challenge in the clinical tumor treatment,which has brought serious harm to human health.With the rapid development of nanomedicine,the construction of multifunctional nano-carriers which can effectively inhibit tumor growth has become the main research direction.Photodynamic therapy(PDT)has emerged as a promising tumor modality,which has unique advantages in selectivity and minimally invasive compared with traditional radiotherapy and chemotherapy.Although the ROS produced by PDT has a certain inhibitory effect on cancer cells,the ineffectiveness of PDT and the complex immunosuppressive microenvironment of the tumor site limit the treatment of tumors.Therefore,it is an effective way to improve the anti-tumor efficiency of photodynamic therapy through the construction of nano-platform combined with photothermal therapy or immunotherapy.First of all,in view of the fact that the reaction catalyzed by the semiconductor material Mo S₂to produce ROS is a non-specific reaction(such as hydrogen production,oxidation and oxygen reduction),according to the relevant literature,when additional catalysts are added to the lamellar Mo S₂,the production efficiency of ROS will be greatly improved.Therefore,in the second chapter,we constructed the lamellar Mo S₂ coated gold nanoparticles platform(Au-Mo S₂@chitosan).Through the combination of gold nanoparticles and lamellar Mo S₂,the nanomaterials not only have the ability of photothermal conversion,but also interact with cancer cells by producing ROS,so as to achieve better therapeutic effect.The obtained Au-Mo S₂@chitosan nanoparticles with a particle size of about 68 nm,have good solution stability and thermal stability.According to the CCK-8 detection of cells,under the condition of dark treatment,Au-Mo S₂@chitosan has less cytotoxicity to cells,but under the condition of light,it can play a strong killing effect on cancer cells.In the in vitro ROS detection experiment,it can also be seen that Au-Mo S₂@chitosan has the ability to produce a certain amount of ROS,combined with its photothermal therapy,can play a stronger inhibitory effect on cancer cells.PDT is a clinical cancer treatment modality based on the induction of therapeutic ROS,which can trigger immunogenic cell death(ICD).With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels,we designed a serum albumin(“SA”)-coated boehmite(“B”;aluminum hydroxide oxide)organic-inorganic scaffold that could be loaded with chlorin e6(Ce6),a photosensitizer,and a honey bee venom melittin(MLT)peptide,denoted Ce6/MLT@SAB.Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm.Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT,while providing MLT-enhanced PDT anti-tumor effects in vitro.Compared with Ce6@SAB,Ce6/MLT@SAB improved Ce6penetration of cancer cells both in vitro and in vivo,thereby providing enhanced intracellular ROS generation with 660 nm light treatment.Following phototreatment,Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells.In the absence of laser irradiation,multi-dose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%,compared to controls.When combined with laser irradiation,a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice.The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented anti-tumor effects,generating increased numbers of CD4⁺and CD8⁺T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.