多功能稀土上转换发光纳米体系的制备及其生物成像和治疗应用研究
发布时间：2023-03-14 18:37
纳米科学技术的进步帮助人类解决了很多个人和社会问题。癌症是严重的全球健康问题之一,亟需找到有效的诊断和治疗方法,如果早期不能对该疾病的诊断和治疗进行有效的控制,今后该疾病的新发病率可升至惊人的数字。目前,通过单一治疗方式可能尚无法实现成功抗癌,因此,多模式疗法和诊断的协同作用对于抗击癌症至关重要。而纳米复合材料可以结合单个纳米平台各自的诊断、治疗优势,是未来解决癌症早期诊断、治疗及相关问题的有效手段之一。因此,本论文成功构建了两种基于上转换发光纳米粒子的新型多功能稀土复合纳米诊断-治疗剂和一种近红外光诱导可降解的锑纳米材料,系统开展了纳米复合材料在生物成像和治疗方面的应用研究。具体包括以下几方面:1、基于稀土上转换发光纳米粒子-黑磷纳米片的纳米复合物用于生物成像和光热/光动力协同治疗我们成功合成了多功能的治疗-诊断纳米复合材料,并应用于体外协同光热/光动力治疗和双模态成像(上转换发光和磁共振成像)。首先,分别采用热裂解和液相剥离法,合成核壳型上转换发光纳米粒子NaYF4:Yb,Er@NaGdF4(UCNP)和黑磷纳米片(BPNS),然后将UC...
【文章页数】：144 页
【学位级别】：博士
【文章目录】：
摘要
ABSTRACT
Chapter 1 Introduction and literature review
1.1 Back ground of the study
1.2 Objectives and motivation of the work
1.3 Literature review
1.3.1 Upconversion nanoparticles
ⅰ. Basic components of upconversion Nanoparticles (UCNPs)
ⅱ. Basic mechanisms of upconversion
1.3.2 Photodynamic therapy (PDT)
1.3.3 Photothermal therapy (PTT)
1.3.4 Black phosphorus as phototherapeutic agent
1.3.5 Antimony as photothermal agent
Chapter 2 Experimental methods and characterization technique
2.1 Chemicals, reagents and materials
2.2 Methods of synthesis
2.2.1 Synthesis of Upconversion nanoparticles (UCNPs)
2.2.2 Synthesis of black phosphorus nanosheets
2.2.3 Synthesis of Antimony nanoparticles based drug delivery system
2.2.4 Surface modification and conjugation
2.3 Characterization and measurement
2.3.1 Fluorescence spectrometer
2.3.2 Transmission Electron Microscopy (TEM)
Chapter 3 Nanocomposite from upconversion nanoparticles and black phosphorusnanosheets for bioimaging and therapy
3.1 Introduction
3.2 Experimental procedures
3.2.1 Synthesis of core and core- shell Upconversion nanoparticles
3.2.2 Synthesis of PAA modified Upconversion nanoparticles
3.2.3 Synthesis of black phosphorus nanosheet
3.2.4 Synthesis of PEG modified black phosphorus nanosheet (BPNS)
3.2.5 Combination of UCNP-PAA with BPNS-NH2(denoted as UCNP-BPNS)
3.2.6 Instruments and devices used for Characterizations
3.2.7 Laser-induced photothermal (PTT) effects
3.2.8 Singlet Oxygen Detection
3.2.9 In vitro cytotoxicity Assay
3.2.10 Live/dead staining of HeLa cells after exposure to UCNP-BPNS
3.2.11 Upconversion luminescence imaging in vitro
3.2.12 Magnetic resonance (MR) imaging
3.3 Result and discussion
3.3.1 Synthesis and characterizations of UCNP-BPNS
3.3.2 Photothermal therapy (PTT) effect
3.3.3 Photodynamic therapy (PDT) effect
3.3.4 Cytotoxicity In vitro
3.3.5 In vitro UCL imaging
3.3.6 T1-weighted magnetic resonance (MR) imaging
3.4 Summary
Chapter 4 Near-infrared laser induced degradable antimony nanoparticle baseddrug delivery system for synergistic chemo-photothermal therapy
4.1 Introduction
4.2 Experimental procedures
4.2.1 Synthesis of antimony nanoparticles (AMNP)
4.2.2 DOX loading
4.2.3 Synthesis of PAA modified AMNP-DOX (AMNP-DOX-PAA)
4.2.4 Instruments and devices used for Characterizations
4.2.5 Laser-induced Photothermal Therapy (PTT) of AMNP-DOX-PAA
4.2.6 DOX release of AMNP-DOX-PAA
4.2.7 In vitro cytotoxicity assay
4.2.8 Live/dead staining of HeLa cells after exposure to the samples
4.3 Computational Methodology used to investigate degradability of antimony
4.4 Result and discussion
4.4.1 Synthesis and characterizations of AMNP-DOX-PAA
4.4.2 Photothermal therapy (PTT) effect
4.4.3 Laser induced degradability of AMNP
4.4.4 Computational result about degradability of AMNP
4.4.5 DOX loading and release profile (Chemo-Therapy)
4.4.6 Cytotoxicity In vitro
4.5 Summery
Chapter 5 Core-shell nanostructure from rare-earth doped upconversionnanoparticle coated with antimony for dual-mode imaging-mediated photothermaltherapy
5.1 Introduction
5.2 Experimental section
5.2.1 Synthesis of Nd3+ sensitized UCNP(NaYF4:Yb,Er@NaYF4:Yb,Nd@NaGdF4:Nd)
5.2.2 Removing oleic acid from the surface of the UCNPs
5.2.3 Coating antimony nanoshell over the surface of the OA-free UCNPs
5.2.4 Surface modification of UCNP@Sb with DSPE-PEG
5.2.5 Instruments and devices used for characterizations
5.2.6 Photothermal conversion capability of UCNP@Sb-PEG resulting PTT effect
5.2.7 T1-weighted magnetic resonance (MR) imaging
5.3 Results and discussion
5.3.1 Characterization of the nanostructures
5.3.2 Photodegradability of antimony and recovery of UCL intensity of UCNP@Sb-PEG
5.3.3 Application of UCNP@Sb-PEG for PTT
5.3.4 UCNP@Sb-PEG as T1-weighted MR imaging contrast agent
5.4 Summery
Chapter 6 Conclusions and future perspective
6.1 Conclusions
6.2 Future perspectives
REFERENCES
AUTHOR PUBLICATIONS
AUTHOR PATENT
ACKNOWLEDGEMENTS
本文编号：3762530
【文章页数】：144 页
【学位级别】：博士
【文章目录】：
摘要
ABSTRACT
Chapter 1 Introduction and literature review
1.1 Back ground of the study
1.2 Objectives and motivation of the work
1.3 Literature review
1.3.1 Upconversion nanoparticles
ⅰ. Basic components of upconversion Nanoparticles (UCNPs)
ⅱ. Basic mechanisms of upconversion
1.3.2 Photodynamic therapy (PDT)
1.3.3 Photothermal therapy (PTT)
1.3.4 Black phosphorus as phototherapeutic agent
1.3.5 Antimony as photothermal agent
Chapter 2 Experimental methods and characterization technique
2.1 Chemicals, reagents and materials
2.2 Methods of synthesis
2.2.1 Synthesis of Upconversion nanoparticles (UCNPs)
2.2.2 Synthesis of black phosphorus nanosheets
2.2.3 Synthesis of Antimony nanoparticles based drug delivery system
2.2.4 Surface modification and conjugation
2.3 Characterization and measurement
2.3.1 Fluorescence spectrometer
2.3.2 Transmission Electron Microscopy (TEM)
Chapter 3 Nanocomposite from upconversion nanoparticles and black phosphorusnanosheets for bioimaging and therapy
3.1 Introduction
3.2 Experimental procedures
3.2.1 Synthesis of core and core- shell Upconversion nanoparticles
3.2.2 Synthesis of PAA modified Upconversion nanoparticles
3.2.3 Synthesis of black phosphorus nanosheet
3.2.4 Synthesis of PEG modified black phosphorus nanosheet (BPNS)
3.2.5 Combination of UCNP-PAA with BPNS-NH2(denoted as UCNP-BPNS)
3.2.6 Instruments and devices used for Characterizations
3.2.7 Laser-induced photothermal (PTT) effects
3.2.8 Singlet Oxygen Detection
3.2.9 In vitro cytotoxicity Assay
3.2.10 Live/dead staining of HeLa cells after exposure to UCNP-BPNS
3.2.11 Upconversion luminescence imaging in vitro
3.2.12 Magnetic resonance (MR) imaging
3.3 Result and discussion
3.3.1 Synthesis and characterizations of UCNP-BPNS
3.3.2 Photothermal therapy (PTT) effect
3.3.3 Photodynamic therapy (PDT) effect
3.3.4 Cytotoxicity In vitro
3.3.5 In vitro UCL imaging
3.3.6 T1-weighted magnetic resonance (MR) imaging
3.4 Summary
Chapter 4 Near-infrared laser induced degradable antimony nanoparticle baseddrug delivery system for synergistic chemo-photothermal therapy
4.1 Introduction
4.2 Experimental procedures
4.2.1 Synthesis of antimony nanoparticles (AMNP)
4.2.2 DOX loading
4.2.3 Synthesis of PAA modified AMNP-DOX (AMNP-DOX-PAA)
4.2.4 Instruments and devices used for Characterizations
4.2.5 Laser-induced Photothermal Therapy (PTT) of AMNP-DOX-PAA
4.2.6 DOX release of AMNP-DOX-PAA
4.2.7 In vitro cytotoxicity assay
4.2.8 Live/dead staining of HeLa cells after exposure to the samples
4.3 Computational Methodology used to investigate degradability of antimony
4.4 Result and discussion
4.4.1 Synthesis and characterizations of AMNP-DOX-PAA
4.4.2 Photothermal therapy (PTT) effect
4.4.3 Laser induced degradability of AMNP
4.4.4 Computational result about degradability of AMNP
4.4.5 DOX loading and release profile (Chemo-Therapy)
4.4.6 Cytotoxicity In vitro
4.5 Summery
Chapter 5 Core-shell nanostructure from rare-earth doped upconversionnanoparticle coated with antimony for dual-mode imaging-mediated photothermaltherapy
5.1 Introduction
5.2 Experimental section
5.2.1 Synthesis of Nd3+ sensitized UCNP(NaYF4:Yb,Er@NaYF4:Yb,Nd@NaGdF4:Nd)
5.2.2 Removing oleic acid from the surface of the UCNPs
5.2.3 Coating antimony nanoshell over the surface of the OA-free UCNPs
5.2.4 Surface modification of UCNP@Sb with DSPE-PEG
5.2.5 Instruments and devices used for characterizations
5.2.6 Photothermal conversion capability of UCNP@Sb-PEG resulting PTT effect
5.2.7 T1-weighted magnetic resonance (MR) imaging
5.3 Results and discussion
5.3.1 Characterization of the nanostructures
5.3.2 Photodegradability of antimony and recovery of UCL intensity of UCNP@Sb-PEG
5.3.3 Application of UCNP@Sb-PEG for PTT
5.3.4 UCNP@Sb-PEG as T1-weighted MR imaging contrast agent
5.4 Summery
Chapter 6 Conclusions and future perspective
6.1 Conclusions
6.2 Future perspectives
REFERENCES
AUTHOR PUBLICATIONS
AUTHOR PATENT
ACKNOWLEDGEMENTS
本文编号：3762530
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