Controllable Synthesis Of Multifunctional Two-Dimensional Nanomaterials For Tumor Theranostics

The increasing demand of clinical biomedicine and fast development of nanobiotechnology has substantially promoted the generation of a variety of organic/inorganic nanosystems for biomedical applications.Biocompatible two-dimensional(2D)nanomaterials,have emerged as a new unique family of nanomaterials that show unprecedented advantages and superior performances in tumor theranostics due to their unique compositional,structural and physicochemical features.In this dissertation,three nano-theranostics systems were constructed by using the fluorescence quenching ability,photothermal and photodynamic characteristics of two-dimensional materials through controllable assembly,which realized specific diagnosis and multimode synergistic treatment of tumor.The main contents of the dissertation are as follow:1.2D ultrathin Pd NSs with uniform size,excellent fluorescence quenching efficiency and photothermal performance was synthesized.Based on the uniform-sized Pd NSs,we constructed a fluorescent biosensor for detecting circulating tumor DNA(ctDNA)by utilizing the different affinities of Pd NSs towards ssDNA versus dsDNA,and combining with its high-efficiency quenching ability related to the distance of the fluorophore.We designed a pair of fluorescent detection probes with DNA single-stranded toehold structures.In the absence of target DNA,the strong interaction between the single-stranded toehold structures and Pd NSs made the DNA detection probes adsorb to the surface of Pd NSs,resulting in effective fluorescence quenching.In the presence of target DNA,it can be linked by T4 DNA ligase to form long DNA duplex structures,which displayed weak affinity toward Pd NSs,producing the fluorescence recovery.The remarkable fluorescence quenching efficiency and ssDNA/dsDNA differential affinity of Pd NSs made it have a good detection ability without signal amplification.The result indicated that this facile but cost-effective strategy holds great promise in tumor diagnoises.2.A new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO2 nanosphere(H-MnO2)was demonstrated for achieving not only nucleus-targeted NIR-? photothermal therapy(PTT),but also tumor microenvironment(TME)hypoxia relief enhanced photodynamic therapy(PDT).The Pd@Au nanoplates presented a photothermal conversion efficiency(PTCE)as high as 56.9%,superior to those PTAs activated in the NIR-? region such as Cu9S5 nanoparticles(37%),Cu3BiS3 nanorods(40.7%),and Au/Cu2-xS nanocrystals(43.2%).They further functionalized with TAT moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO2(?100 nm)loaded with photosensitizer Ce6(TAT-Pd@Au/Ce6/PAH/H-MnO2)to construct a hierarchical targeting nanoplatform.The as-made TAT-Pd@Au/Ce6/PAH/H-MnO2 demonstrated good premature renal clearance escape ability and increased tumor tissue accumulation.It could be degraded in acidic TME and generate O2 by reacting to endogenous H2O2 to relieve the hypoxia for enhanced PDT,while the released small TAT-Pd@Au nanoplates could effectively enter the nucleus to mediate PTT.As a result,we achieved a remarkable therapeutic effect owing to the synergistic PTT/PDT therapy.This hierarchical targeting,TME-responsive,cytoplasm hypoxia relief PDT and nuclear NIR-? PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.3.A near-infrared(NIR)-responsive 2D Ti3C2/g-C3N4 heterostructure was designed for in situ oxygen-generating enhanced multimode PDT and photothermal therapy(PTT).We demonstrated that the assembly of Ti3C2 to g-C3N4 significantly extend the absorption of g-C3N4 to NIR region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation compared to free g-C3N4.After further modification of triphenylphosphonium bromide(TPP)on Ti3C2/g-C3N4,and the mitochondria-targeting Ti3C2/g-C3N4-TPP enables produce oxygen-independent ·O2-and ·OH through electron transfer.Moreover,it also achieved oxygen self-supplement 1O2 generation through energy transfer on account of its ability of photocatalytic split endogenous water.As a result,a multimode enhanced PDT was performed under both normoxic and hypoxic conditions.Ti3C2/g-C3N4-TPP also shows good photothermal performance derived from Ti3C2 for PTT.This work expands the g-C3N4-based PDT application,contributing to design photocatalytic nanomaterials with desired absorption to overcome the limitation of tumor hypoxia.