Construction Of Multifunctional Nanosystems For Tumor Phototherapy

Cancer is currently a major and critical disease that seriously threatens human health.Traditional cancer treatments often suffer from trauma,poor controllability,inefficiency,significant side effects,and easy relapse.In order to make up for the shortcomings of traditional therapies,phototherapy that based on photodynamic therapy(PDT)and photothermal therapy(PTT)came into being.Because of the good spatiotemporal controllability and basically non-invasive characteristics,phototherapy is widely studied and regarded as a promising new tumor treatment method.However,traditional phototherapy drugs are mainly composed of small hydrophobic compounds,and their pharmacokinetics in vivo are often poor and lack tumor targeting.In addition,in practical applications,the conventional PDT or PTT mode is often affected by the complex tumor environment in the body,which seriously affects the actual effect.For example,the hypoxic intratumoral atmosphere will seriously reduce the efficacy of oxygen-dependent PDT,and the inflammatory responses caused by high temperature after PTT is also an important barrier that hinders its clinical application.Thanks to the vigorous development of nanotechnology,more and more new nanomaterials have been developed and prepared for the realization of safe and efficient tumor phototherapy.By rationally modifying functionalized nanomaterials,the biocompatibility of the materials can be greatly improved and they can be enriched with functions,thereby achieving a powerful enhancement of the existing phototherapy model.Based on this,this paper designed and constructed a series of multifunctional tumor phototherapy nano-systems for efficient tumor suppression and reducing the side effects of treatment.The specific research contents are as follows:In chapter one,we made a brief description of the basic concepts and research status of tumor phototherapy.It focuses on the construction of the nano-phototherapy system and the problems and solutions in the current research.In chapter two,the photosensitizer chlorin e6(Ce6)was loaded on tungsten nitride(WN)nanoparticles and modified with folic acid(FA)to build an oxygen self-supplying nanometer platform FA-WN-Ce6(FWC)for efficient PDT aganist hypoxic tumors.Through the specific recognition of FA,FWC can target the tumor site and produce oxygen by photolysis of water under 630 nm light to provide sufficient oxygen supply for Ce6-mediated PDT,and then achieve efficient PDT effect in hypoxic tumor.In addition,the oxygen produced by FWC can also reduce the level of hypoxia in the tumor,thereby reducing the degree of tumor invasion and metastasis.In Chapter three,functionalized nanosystem based on partially oxidized tin sulfide(POS)nanosheets are constructed to achieve efficient tumor suppression and inflammation elimination.The POS-loaded chemotherapeutic drug doxorubicin(DOX)modified by a tumor-targeting polymer(PEG-c RGD peptide,PEG-c RGD)was used to obtain the product Polymer@POS@DOX,or PPOSD.PPOSD can achieve c RGD-mediated specific tumor recognition after intravenous injection in vivo.Under the irradiation of 561 nm laser,the POS part of PPOSD can photocatalyze the reduction of endogenous carbon dioxide(CO₂)to obtain carbon monoxide(CO)which sensitizing the therapeutic effect of DOX.Under the light of 808 nm,the POS part can also be used as a photothermal agent for photothermal conversion to achieve the purpose of PTT.In addition,the previously produced CO can effectively weaken the inflammatory response caused by PTT.The good synergy of chemotherapy,PTT and CO can bring safe and efficient tumor treatment and reduce the potential side effects of PTT.In Chapter four,a nano-reactor P@DW/BC with near-infrared light responsiveness was prepared to simultaneously achieve tumor PTT and CO-mediated inflammation elimination under single laser irradiation.Defective tungsten oxide(DW)nanosheets were modified with bicarbonate(BC)by coordinating chemistry to obtain PEG@DW/BC(P@DW/BC).Under the single 808 nm laser irradiation,DW acts both as a photothermal agent to achieve photothermal conversion and as a photocatalyst to reduce CO₂ to produce CO.It is worth mentioning that BC can quickly decompose to produce CO₂ at the high temperature during PTT to enhance the photocatalytic reduction process of CO.Thanks to the excellent heat production and CO generation capacity,PPOSD can simultaneously achieve effective tumor elimination and reduce the level of PTT-induced inflammation response under a single near-infrared light irradiation,and finally achieve long-term and efficient tumor suppression.