| Tumor is a kind of disease characterized by clonal proliferation of cells,whose growth and differentiation is out of control at the gene level because of repeated stimulation of tumorigenic factor. Some tumors are called malignant tumors which are aggressive and strong as well as rapid progress, easy to transfer, known as cancer. At this stage, annual growth of cancer cases worldwide has reached as many as 14 million, and the number of deaths has reached 8million per year. China, as the most populous country in the world, has the largest number of cancer deaths. The incidence and mortality rates of cancer continue to rise. But it is very difficult to achieve satisfactory results for traditional treatments, such as surgery, radiotherapy and chemotherapy. This situation forces the people to continue the efforts to explore more effective strategies in order to achieve early diagnosis and efficient treatment of cancer. Currently, nanotechnology has been considered as one of the most important technologies in the 21 st century. With the continuous progress of science and technology, nanotechnology has showed great vitality in the multi-disciplinary. The appearance and development of nanotechnology has also brought an unprecedented revolution to contemporary medicine. With the deepening of research,nanotechnology has gradually showed tremendous value in the medical field.Upconversion nanoparticles can be excited under the near-infrared light and emit ultraviolet 、 visible or near-infrared light. This feature gives them a great advantage compared with other luminescent materials in the biomedical field, such as no photobleaching, weak background interference, deep tissue penetration as well as little biological tissue damage. in addition, upconversion nanoparticles themselves also have high chemical stability and low toxicity. These characteristics give them a wide range of applications in biomedical field. At present, researchers have conducted extensive studies in a number of biomedical applications, such as biological imaging,biosensors, photodynamic therapy, photothermal therapy, drug delivery, etc.Meanwhile, people have also noted some problems of upconversion nanoparticles inbiomedical applications. For example, people think about how to improve tumor targeting, how to improve the yield of singlet oxygen in photodynamic therapy in order to obtain a better therapeutic effect, and how to combine tumor imaging and photodynamic therapy organically, and so on.In this paper, based on future clinical utility, we followed the clue of constructing upconversion nanoplatform, and focused on the characteristics of the biological safety, diagnostic specificity and the efficiency and targeting of treatment.And the strategy of diagnosis and treatment of cancer had been further developed.Methods(1)We prepared high quality hexagonal phase upconversion nanoparticles and transferred the nanoparticles from hydrophobic to hydrophilic using ligand exchange method.We analyzed the characterization of particle size and morphology of bare UCNPs、 UCNP-AEP、UCNP-PAA and UCNP-PAAm using transmission electron microscopy(TEM).Moreover, the infrared spectral, hydrodynamic diameter and zeta potential of all kinds of UCNPs were analyzed.( 2) Using confocal imaging and standard MTT analysis methods, We have systematically investigated the cellular enrichment and cytotoxicity of upconversion nanoparticles modified by different ligands with NIH-3T3 and MCF-7 cells.(3)We constructed the core-shell structure of Na YF4: Yb3 +, Er3+/ Na YF4: Yb3 +,Tm3+nanoparticles through the surface shell coating and further improved the conversion luminous efficiency; C60 MA photosensitizer was loaded through covalent coupling, then its stability and carrying capacity were increased,the distance of energy transfer was shorten, and the yield of singlet oxygen was improved.PEG modification reduced the cell toxicity, increased biocompatibility.Then the nano photosensitive platform with integration of diagnosis and treatment was constructed.( 4) In the aspects of diagnosis, treatment effects and biological safety of malignant tumors, we went on a systematic study for the multi functional upper conversion nano platform. According to the experimental results at the cellular level,and in vivo imaging and photodynamic killing,we made an objective evaluation for treatment of the mice and biological safety of nano photosensitive platform.Results( 1) Having analysed the characterization of UCNPs, we could know that Na YF4:Yb3+,Er3+ nanoparticles had many special characteristics such as good dispersibility, uniform particle size distribution, good crystalline property and high luminescent efficiency.And after the surface modification,UCNPs showed excellent stability and good water solubility.( 2) Four Na YF4: Yb3+, Er3+ with different surface ligands and charges(bare ucnps, UCNP-AEP, UCNP-PAA and UCNP-PAAm), although their size, water soluble and upconversion luminescence efficiency were very similar, their cellular uptake and cytotoxicity was different. UCNPs- PAAm had the highest cell uptake rate and a higher cytotoxicity( 3) At the excitation of the continuous wave light source in 980 nm,UCL appeared at 475 nm, 650 nm, 540 nm, and 808 nm band. 808 nm emission could be used for high contrast imaging, and other bands were able to transfer the energy to C60 MA in order to trigger PDT.(4)From what had been discussed in diagnosis and treatment of cancers,we might safely come to the conclusion that the multifunctional upconversion nano platform not only realized PDT guided by high-contrast imaging of a single excitation wavelength,but also showed sensitive diagnostic specificity, targeting and treatment efficiency.The results of the study on the biological safety showed that the method of diagnosis and treatment, which was mediated by the nano photosensitive platform, had high biological safety for the main organs and blood system of the organism.ConclusionThe core-shell Na YF4:Yb3+,Er3+/Na YF4:Yb3+,Tm3+UCNPs,whose photosensitizer was fullerenes(C60MA), could solve the conflicts between high yield of singlet oxygen required for PDT and high contrast imaging at the same time. When it met the PDT treatment, it could realize 808 nm imaging of a single excitation wavelength and obtain photodynamic therapy guided by high-contrast imaging.And itsuccessfully combined tumor imaging and photodynamic therapy organically.Moreover,in the diagnosis and treatment of malignant tumors, NCUPs(Yb, Er, Tm)- C60 MA platform had showed sensitive diagnostic specificity, targeting and treatment efficiency, and high biological safety. |
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