Tumor-Associated Macrophage Membrane-Coated Upconversion Nanoparticles For Improved Photodynamic Immunotherapy

With the rapid development of nanotechnology,because of the advantageous properties(e.g.,relatively high drug loading content,controllable drug release,excellent passive and active targeting,good stability,biodegradability,biocompatibility,and low toxicity),and nanomaterials have been widely developed for the treatment of potential of photothermal and photodynamic therapies for cancer.With the in-depth research of nanomedicine,surface modification and functionalization of nanoparticles has become the main research direction of cancer treatment.For example,superparamagnetic iron oxide nanoparticles(Ferumoxytol)was a novel nanomaterial drugs for leukemia therapy through ferroptosis induced by ROS mechanism;carbon-dot-supported atomically dispersed gold as a promising agent for anticancer applications,which has good anticancer effect and biological safety;the photothermal conversion efficiency of copper sulfide can be used for photothermal treatment.In addition,upconversion nanoparticles(UCNPs)usually containing lanthanide ions are able to convert long-wavelength near-infrared(NIR)light with greatly improved tissue penetration into short-wavelength light through a multiphoton absorption/single-photon emission process.And the strategy of UCNP-based PDT in combination with immunotherapy which strong antitumor immunities can been generated to inhibit tumor metastasis.In this dissertation,we synthesized and constructed tumor-associated macrophage membrane-Coated upconversion nanoparticles for improved photodynamic immunotherapy.Specific research results are as follow:1.Upconversion nanoparticles(UCNPs)as a new generation of fluorescent materials have the advantages of high luminous intensity,narrow emission band,good stability,high biocompatibility,low toxicity,and which are able to convert long-wavelength near-infrared(NIR)light(700-1000 nm)with greatly improved tissue penetration and reduced photo-damage.Therefore,UCNPs have shown promising applications in photodynamic therapy(PDT).In particular,the surface modification of UCNPs can be designed to photosensitizer loading and the excitation source is strongly absorbed by the photosensitizer.Subsequently,the toxicity of singlet oxygen generated by the excited photosensitizer causes oxidative damage to tumor cells.the strategy of UCNP-based PDT can overcome the limitations of traditional photosensitizers(PS),and PDT in combination with immunotherapy can produce synergistic effects.In summary,we selected designed and developed novel multifunctional Na YF₄:Yb,Er with good photostability as the carrier,covalently modified the photosensitizer Rose Bengal,and modified the tumor-associated macrophage membrane(NPR@TAMM)on surface.We perform a series of characterizations on the structure,cell uptake,targeting,and cell-level photodynamic therapy detection of new inorganic/biological functional composite material.2.Based on previous studies,we successfully synthesized a TAM membrane-coated upconversion nanoparticle with photosensitizer conjugating(NPR@TAMM)system and performed in vitro therapeutic characterization.Furthermore,we established cancer mouse model of primary tumor and metastatic tumor,and set up different groups to evaluate the therapeutic effect of the new composite material.At the same time,we detected immune cell activity,tumor cytokine content,and marker expression in tumor microenvironment,and test the biosafety of nanomaterials in vivo.The synthesized NPR@TAMM nanocomposites are regarded as nanotheranostic agents for tumor-related macrophage membrane guided synergetic photodynamic/immunotherapy.