Functionalized Nanostructures Based on Rare-Earth Doped Upconversion Luminescence Nanoparticles for Bioimaging and Synergistic Therapy

Author:Solomon Tiruneh Dibaba

Supervisor:ren wei sun li ning

Database:Doctor

Degree Year:2019

Download:37

Pages:144

Size:10068K

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Advances in nanoscience and technology have helped humans to solve many personal and social problems.Cancer is one of the serious global health problems that need urgent and effective diagnosis and treatment methods.If the disease cannot be effectively controlled in the early stage using convenient diagnosis and therapeutic methods,the new incidence of the disease can rise to an alarming number in the future.At present,successful anti-cancer is not yet achieved by a single treatment method,so the synergy between multimodal therapies and diagnosis is critical to combating cancer.Nanocomposites can combine the diagnostic and therapeutic advantages of individual nano-platforms,and are one of the effective methods to solve early cancer diagnosis,treatment,and related problems in the future.Therefore,this thesis successfully developed two novel multifunctional nano-diagnostic-therapeutics composites based on rare-earth doped up-converting luminescence nanoparticles and applied for bioimaging and therapy.In addition,near-infrared(NIR)laser induced degradable antimony nanoparticle based drug delivery system was synthesized and used for synergistic chemo-photothermal therapy.Specifically,the following aspects are included:1.Theranostic nanocomposite from upconversion luminescent nanoparticles and black phosphorus nanosheetsIn this part,the multifunctional theranostic nanocomposite(UCNP-BPNS)was synthesized from upconversion nanoparticles(UCNP)and black phosphorus nanosheets(BPNS)for synergistic photothermal/photodynamic therapies in vitro and dual modal imaging.Core-shell UCNP(NaYF4:Yb,Er@NaGdF4)and BPNS were synthesized using solvo-thermal and liquid exfoliation methods,respectively,and then covalently conjugated after UCNP being modified with polyacrylic acid and BPNS with methoxypolyethylene glycol amine.The experimental results show that about 85%of HeLa cells incubated with the nanocomposite were killed upon 808 nm laser irradiation,endorsing apparent heat conversion effect of BPNS that exhibited good photothermal therapeutic(PTT)effect of the UCNP-BPNS on the cancer cells.In addition,under 980 nm laser irradiation,HeLa cells incubated with UCNP-BPNS have a survival rate of only about 29%due to the Forster resonance energy transfer(FRET)from UCNP to BPNS that generate cytotoxic singlet oxygen(1O2),resulting good photodynamic therapeutic(PDT)effect of the nanocomposite.The synergistic PTT/PDT therapeutic effect provided by UCNP-BPNS under simultaneous 808 and 980 nm laser irradiation that destroyed about 91%of the HeLa cells was significantly higher than either PTT or PDT alone.In addition,the nanocomposites exhibit good magnetic resonance imaging and upconversion luminescence imaging.These results indicate that UCNP-BPNS simultaneously exhibits dual-mode imaging and synergistic treatment.2.Near-infrared laser induced degradable antimony nanoparticle based drug delivery system for synergistic chemo-photothermal therapyFirstly,good mono-dispersed antimony nanoparticles(AMNP)were synthesized using simple and cost effective method.And the anticancer doxorubicin hydrochloride(DOX)was loaded by electrostatic interaction,and then modified with polyacrylic acid(PAA)to improve its biocompatibility.The experimental results reveal that under NIR(808 nm)laser irradiation of AMNP-DOX-PAA,not only high photothermal conversion efficiency of AMNP was achieved but also a pH dependent DOX release was enhanced due to laser induced hyperthermia.As a consequence,almost all of HeLa cells(around 97%)were killed due to combined effect of chemotherapy and photothermal therapy.More interestingly,AMNP showed very fast laser-induced degradability(degraded in about 10 minutes),so that the nanosystem can be degraded from the body in a short time and hence significantly minimizes long term toxicity after synergistic chemo-photothermal therapy.In addition,we use the density functional theory(DFT)to calculate the system and analyze the mechanism of degradation of AMNP.It suggests that the NIR laser irradiation can induce a phototherm ally activated reaction at the surface of AMNP in water,which can lead to surface degradation via formation of Sb-H bonds first and then Sb-OH bonds upon further increase of temperature.3.Core-shell nanostructure from rare-earth doped upconversion nanoparticle coated with antimony for dual-mode imaging-mediated photothermal therapy using single NIR laserMotivated with good photothermal conversion efficiency and photodegradability of antimony nanoparticle based drug loading system studied in Part 2,we expect to design nano-diagnostic-therapeutic agents from combination of rare-earth doped up-converting luminescence nanoparticles and antimony.Therefore,in this section,we first synthesized the core-shell-shell structure of upconversion luminescence nanoparticles NaYF4:Yb,Er@NaYF4:Yb,Nd@NaGdF4:Nd(UCNP),and then used seed-mediated method to grow antimony shell on the surface.Finally,the UCNP@Sb nanoparticles were modified with DSPE-PEG to afford good water solubility,and named as UCNP@Sb-PEG.The experimental results show that UCNP@Sb-PEG exhibits high photothermal conversion efficiency under 808 nm laser excitation,and the antimony shell degrades with the prolongation of laser irradiation time,so that the upconversion luminescence of UCNP can be recovered.So the UCNP@Sb-PEG can be used for upconversion luminescence imaging.In addition,the presence of rare earth Gd elements offer the UCNP@Sb-PEG a good property of magnetic resonance imaging.Currently,relevant biological application experiments of the system are in progress.