Preparation And Cancer Therapeutic Properties Of NIR Light Responsive G-C₃N₄ Based Nanocomposites

As a typical photochemical therapy,photodynamic therapy(PDT)involves the use of specific light to stimulate non-toxic photosensitive compounds to produce reactive oxygen species(ROS)to kill malignant/diseased cells.The novel near-infrared(NIR)photoexcited PDT based on upconversion nanoparticles(UCNPs)and photosensitizer nanocomposites have the following unique advantages:(1)808 nm or 980 nm NIR light as an excitation source,can obviously increase tissue penetration depth;(2)UCNPs self-fluorescence is greatly reduced,signal-to-noise ratio and imaging sensitivity are distinctly improved;(3)Some efficient but hydrophobic photosensitizer can be directly loaded into UCNPs-based nanocarriers for targeted PDT.Therefore,the relevant research has attracted the attention of global experts and scholars.As a potential newly two-dimensional layered photosensitizer,graphite-phase carbon nitride exhibits excellent biocompatibility,high blue photoluminescence quantum yield and physicochemical stability.The purpose of this paper is to design and synthesize NIR responsive g-C3N4 based upconversion nanocomposites for multi-mode imaging guided highly efficient tumor diagnosis and treatment,and to investigate their biological properties as photosensitive drugs,the main research contents are as follows980 nm NIR-responsive two-dimensional layered g-C3N4/UCNPs and 808 nm NIR-respomsive core-shell structured UCNPs@g-C3N4-PEG(PEG is polyethylene glycol)nanocomposites were prepared by liquid phase stripping method and template method,respectively.The ultraviolet-visible(UV-vis)light generated by UCNPs irradiated upon NIR laser can be effectively transmitted to g-C3N4,which can activate g-C3N4 to generate ROS molecules,to enhance the therapeutic effect of PDT.Due to the emission position of UCNPs completely match with the absorption spectrum of g-C3N4.The blue photoluminescence of g-C3N4 and the up-conversion luminescence property of UCNPs,the nanocomposites have the capability of up/down-conversion fluorescence imaging,the application of nanocomposites in biomedical field has been expanded.Both nanosystems have achieved NIR-responsive imaging guided photodynamic anticancer therapy.Moreover,the structure characteristics and photosensitizer loading capacity,up-conversion luminescence(UCL),computed tomography(CT)and magnetic resonance imaging(MRI)three modality imaging performance of core-shell structured UCNPs@g-C3N4-PEG nanosystem were further studied.Under the synergistic effect of PDT and photothermal therapy(PTT),the nanosystem showed excellent anticancer performance.A novel inorganic dual-photosensitizer nanosystem UCNPs@g-C3N4-Au25-PEG was prepared for the first time,through coating mesoporous g-C3N4 layer on UCNPs core,followed by attaching ultrasmall Au25 nanoclusters and PEG molecule.The UV-vis light and the intensive NIR emission from UCNPs can activate g-C3N4 and excite Au25 nanoclusters to produce ROS,respectively,thus realizing the simultaneous activation of two kinds of photosensitizers for greatly enhanced light utilization and the efficiency of PDT mediated by a single 980 nm NIR laser excitation.Utilizing in vitro and in vivo experiments including cell viability,ROS production and tumor growth inhibition rate in mice,it was further confirmed that the efficacy of PDT for the simultaneous activation of dual-photosensitive drugs by a single NIR laser excitation was significantly higher than that of the single photosensitive drug system.This nanosystem inherent multi-mode imaging(UCL,CT and MRI)performance enables it to achieve image-guided treatment.Firstly,superparamagnetic Fe3O4 nanoparticles were synthesized by hydrothermal method,followed by coating with mesoporous g-C3N4 shell,absorbing ultrasmall UCNPs,and then further modified with PEG molecules,magnetic-targeted optical theranostic nanoplatform Fe3O4@g-C3N4-UCNPs-PEG was constructed.Upon NIR laser irradiation,the UCNPs convert the energy to the g-C3N4 photo sensitizer through fluorescence resonance energy transfer process,thus producing a vast amount of ROS molecules.This nanoplatform enables targeted delivery anticancer drugs under the guidance of an external magnetic field.In vitro and in vivo experiment results revealed that Fe3O4@g-C3N4-UCNPs-PEG nanoparticles can be effectively enriched at tumor site under the action of external magnetic field,with significant tumor growth inhibition effect and without any toxic side effects.Moreover,the inert g-C3N4 layer between Fe3O4 core and outer UCNPs can substantially depresss the quenching effect of Fe3O4 on the upconversion emission,effectively improved photoluminescence performance.This nanosystem also achieved T1/T2-weighted dual-modal MRI guided photodynamic anticancer therapy.A tumor microenvironment responsive UCNPs@MnSiO3@g-C3N4-PEG nanoplatform was prepared by in situ growth method.Utilizing mesoporous manganese silicate coated UCNPs as nanocarriers,for loading blue photoluminescent g-C3N4 quantum dots to act as photosensitive drug and imaging agent simultaneously.The intracellular glutathione level was reduced by the metal reduction reaction between the high valence manganese ions in UMCNs-PEG nanoparticles and glutathione in the tumor acidic microenvironment,the overexpression of glutathione on photodynamic anticancer therapeutic effect was eliminated.Thereby enhancing the production of ROS molecules and the efficacy of PDT,Mn2+ions are also produced for T1-weighted MRI simultaneously.The inherent UCL,CT and MRI multi-mode imaging performance of as-synthesized nanoparticles was utilized to realize real-time monitoring of the treatment process.