Tumor Photothermal Therapy Based On Multifunctional Nanomaterials

Malignant tumors seriously affect the health and quality of life of patients.At present,the treatment for tumor is still a worldwide medical problem.Due to the individual differences and heterogeneity of tumors,it is difficult to eradicate tumors thoroughly by traditional cancer treatments,and it will cause a series of side effects in the course of treatment.Photothermal therapy(PTT),a new non-invasive cancer treatment technology,has gradually attracted widespread attention.Under the irradiation of near infrared laser,PTT transforms light energy into heat energy through photothermal agents,and produces local high temperature to induce apoptosis or necrosis of tumor cells.This physiotherapy method has many advantages,such as strong penetration,good therapeutic effect and little side effects.Although photothermal therapy has shown broad application prospects in the field of cancer treatment,there are still some problems to be solved urgently,including the ineffective accumulation of photothermal agents in cancer tissues,the presise control of illumination time,and inflammation caused by excessive heat.Based on these considerations,we have carefully designed and prepared a series of photothermal nanocomposites with multiple functions,combined with chemical therapy,photodynamic therapy or hydrogen therapy in order to achieve efficient synergistic therapeutic effect.Detailed works are as follows:In chapter one,we reviewed the types of photothermal agents,including organic nanomaterials,inorganic nanomaterials,and metal nanomaterials.The mechanism of photothermal therapy for tumor was briefly explored and discussed,and the latest researchs on tumor photothermal therapy were summarized.In addition,we also summarized the synergistic therapy based on photothermal therapy,including chemotherapy synergy,photodynamic synergy,immune synergy,and gas therapy synergy.In chapter two,using tungsten nitride(WN)nanoparticles as carriers,we designed a photoacoustic(PA)/computed tomography(CT)dual-mode imaging-mediated nanocomposites,which could be responsed to acidic tumor microenvironment and has been utilized for tumor photothermal/chemical drug synergy therapy.After modified by SH-PEG through the coordination of thiol with tungsten,the water solubility and biocompatibility of WN nanoparticles improved obviously.Due to the excellent photothermal conversion ability of WN and the high atomic number of tungsten elements,the prepared PEG-WN nanoparticles can be used as PA/CT imaging contrast agents to precisely guide in vivo photothermal therapy.Additionally,modified with thiolated(2-hydroxypropyl)-?-cyclodextrin(MUA-CD)on the surface of WN,DOX could be successfully transported to tumor tissues with the aid of cyclodextrin hydrophobic inner chamber to load doxorubicin(DOX).Under the stimulation of acidic tumor microenvironment,DOX effectively released from the nanocomposites and played a role in chemotherapy.X-ray photoelectron spectroscopy(XPS)assays show that the WN nanoparticles are biodegradable,which provides a guarantee for the biosafety of WN nanocomposites(PEG-WN-DOX).In vitro and in vivo experiments indicated that PEG-WN-DOX had excellent synergistic therapeutic effects in inhibiting the growth of tumors.In chapter three,we designed and prepared a carbon nanosphere loaded with cerium oxide(CSCe),and then the CSCe were coated with homologous tumor cell membranes to target tumor tissues for photothermal/photodynamic synergistic therapy.The surface carbon layer of polymer sphere precursor has graphene-like structure after calcination at high temperature.Protecting by surface silicon layer during calcination,the harvested carbon nanospheres exhibited good dispersion and uniform size.Cerium oxide possesses the function of superoxide dismutase(SOD),which could convert the superoxide anions into hydrogen peroxide in tumor cells.Specific proteins on the surface of cell membrane made the encapsulated nanocomposites(MCSCe)actively target to homologous tumor cells,resulting in high accumulation of MCSCe in tumor tissues in vivo.Under the irradiation of near infrared laser,carbon nanospheres converted light energy into heat energy for photothermal therapy.On the other hand,the graphene-like structure on the surface of carbon nanospheres could catalyze hydrogen peroxide to produce hydroxyl radicals with higher cytotoxicity,being utilized to improve photodynamic therapy.In vitro and in vivo experiments confirmed that the high efficiency homologous targeting ability of MCSCe and the good therapeutic effects of photothermal/photodynamic synergistic therapy.This design of composite nanomaterials,which integrates photothermal therapy and photodynamic therapy,provides a reference for the extensive treatment of tumor because of their simplicity and versatility.In chapter four,a biomimetic nanosystem based on polydopamine loaded with aminoborane(mPDAB)was constructed.By actively targeting to tumor tissues,we achieved multiple therapeutic effects of anti-tumor,anti-inflammation and anti-recurrence.Polydopamine(PDA)is an excellent long chain macromolecule material with good biocompatibility and photothermal conversion ability.Aminoborane can be effectively loaded onto the surface of PDA nanoparticles by the surface hydrogen bond.Similarly,after encapsulating cell membrane on the surface of PDA,the high accumulation of nanocomposites in tumor tissues in vivo could be achieved by homologous targeting.During the process of photothermal therapy,PDA mediated local hyperthermia may destroy the integrity of tumor cells and cause the intracellular reactive oxygen species(ROS)release into tumor tissues,resulting in inflammatory responses.Under the stimulation of acidic tumor microenvironment,hydrogen released from aminoborane,which consumed ROS to reduce inflammation.In addition,hydrogen destroyed the balance of oxidative stress in tumor cells to provide gas therapy.As inflammation is the main factor inducing the recovery of dormant tumor cells in vivo,the decrease of inflammatory responses can effectively inhibit the recurrence of tumor.