Nanocarrier Systems Based On Photothermal Therapy For Tumor Combination Therapy

In spite of the swift advancement of medical technology in recent decades,cancer remains a major cause of human mortality.The most popular cancer treatment,conventional chemotherapy,is not able to provide satisfactory and lasting therapeutic effects due to dose limitations,harm to healthy tissue,and drug resistance to cancer cells.Consequently,there is an urgent requirement for a novel approach that can produce a beneficial therapeutic effect at low doses.Attention to photothermal therapy as an ideal tumor treatment has been widely drawn in the arena of anti-tumor nanomedicine.The high temperatures produced by photothermal agents can be controlled to reduce damage to other normal tissues.Temperatures within 41-47°C destroy cell membranes that cause irreversible cell necrosis.Compared to normal tissue,tumor cells have a higher metabolic rate and a worse blood supply.In addition,when hyperthermia is used in combination with other treatments,tumor cells can be killed at lower temperatures（39-42°C）.Among the various methods that trigger photothermal therapy（PTT）,the use of near-infrared lasers has received more attention because the heat energy generated by photothermal agent excitation penetrates biological tissues and has low absorption of blood and other soft tissues.Combination therapy has gradually become a trend in clinical research by overcoming the complex environment of tumors to improve treatment effectiveness.These synergistic therapies target the tumor site more precisely and effectively than any monotherapy or theoretical combination therapy,while also significantly reducing toxic side effects.To minimize the detrimental effects of drugs,we circumvent the chemotherapy side effects,utilize PTT to treat cancer,and augment the potency of CDT with PTT.Therefore,we design smart treatment platforms that enable combination therapies to enhance cancer treatment.The specific contents are as follows:Briefly introducing the materials commonly employed in photothermal therapy,such as inorganic,organic,and composite base materials,the first chapter then delves into the application status and potential for growth of photothermal therapy when combined with other treatments,such as chemodynamic therapy（CDT）,photodynamic therapy（PDT）,and gas therapy.In the second chapter,we design a nanocarrier system based on titanium carbide（Ti₃C₂）as the core porous manganese dioxide（Mn O₂）as the shell.The vector is characterized by targeting ability and sensitive p H/GSH triggering controlled release,thereby enhancing the therapeutic effect under tumor.In this work,a hard template is used to generate a layer of porous Mn O₂ on the surface of Ti₃C₂,which has a certain drug load due to its good specific surface area.Nanostructures can also be introduced into tumor tissue through the EPR effect.Ti₃C₂-Mn O₂ is encapsulated with polyethyleneimine（PEI）after loading the drug,and the organic polymer material hyaluronic acid（HA）with targeting ability is modified outside,which has good physiological stability and non-toxicity.Receptors on the surface of cancer cells can be bound to by it,thus increasing cell absorption.The self-driving intelligent treatment platform has a dynamic protection strategy,improves multiple efficacy and multiple therapies,has no toxic side effects,and realizes the comprehensive treatment effect of cancer.In the third chapter,we designed and constructed a drug delivery platform（DOX@H-Mn O₂-PDA）for hollow manganese dioxide with photothermal properties and biodegradability.We used hollow manganese dioxide（H-Mn O₂）nanoparticles as the matrix of the drug delivery system,loaded the anti-cancer drug DOX into the interior of H-Mn O₂,and then used polydopamine（PDA）as a"valve"to block the pores and wrap the hollow manganese dioxide.The sensitive response of the nanoplatform to GSH was demonstrated by in vitro drug release,and the drug release of the nanoplatform gradually increased as the concentration of GSH increased.In vitro reactive oxygen species experiments have proved that the nanoplatform can generate highly toxic hydroxyl radicals by Fenton-like reactions under physiological conditions.In vivo cell experiments have demonstrated that the nanoplatform can consume GSH,enhance chemokinetic therapy and distinguish between normal cells and tumor cells.And through a combination of chemotherapy,chemokinetics and photothermal therapy,compared with monotherapy,the killing power of cancer cells can be greatly improved.