Synthesis Of Upconversion Nanoparticles And Their Applications In Drug Delivery,Bio-Imaging And Detection

Rare earth-doped upconversion nanoparticles（UCNPs）,capable of converting lower-energy photons into higher-energy photons,are endowed with unique and superior features such as excellent optical and chemical stability,high resistance to photobleaching and low toxicity.In addition,the near infrared radiation（NIR）excitation offers minimal photodamage to biological tissues,greater light penetration depth in tissues as well as negligible autofluorescence.UCNPs are therefore attracting considerable scientific interest in biological field,particularly in biomedical detection,bio-imaging and theranostic nanomedicine.In this thesis,we intend to prepare UCNPs with regular shape,uniform size and good crystallinity,and further convert the hydrophobic surface to a more hydrophilic one through surface functionalization.Then we present a lipophilic cytotoxic prodrug-integrated and polyethylene glycol（PEG）-cloaked UCNP scaffold through a facile one-pot supramolecular approach for simultaneous upconversion luminescent（UCL）imaging and drug delivery.Besides,we have made a tentative exploration in constructing a UCNP-based biosensor.In chapter 1,the basic principle of Ln3+-related upconversion emissions and the crystalline structure of UCNPs are described first.Then the recent advances in synthesis,surface modification and biomedical applications including biological sensing,bio-imaging and theranostics based on UCNPs are reviewed,which will provide theoretical foundation and scientific basis for the preparation of nanoparticles,design and application of UCNP-based drug carrier,as well as biodetection in our work.In chapter 2,NaYF₄:Yb,Er UCNPs with regular morphology,uniform size and hexagonal phase are prepared using thermo-decomposition and solvothermal approaches,respectively.It is found that UCL efficiency of UCNPs synthesized by solvothermal approach is much higher than that by thermo-decomposition.Moreover,various surface modification strategies are employed to improve water-dispersibility and biocompatibility of the nanoparticles,facilitating their further biological multi-functionalization and applications.In chapter 3,a versatile platform for drug loading,in vivo delivery and tumor imaging based on UCNPs is presented.The lipophilic cytotoxic prodrug-integrated and polyethylene glycol（PEG）-cloaked UCNP scaffold is prepared through a facile one-pot supramolecular approach.Choosing 7-ethyl-10-hydroxycamptothecin（SN38）-derived prodrug as a model chemotherapeutic,we show that the prodrug-loaded PEGylated UCNPs produce a stable colloidal system in aqueous solution,and drug loading capacity reaches as high as～12.3 wt%.Besides,a sustained drug release profile is observed,indicating that the drug payloads can be transported to targeted tumor sites via the enhanced permeability and retention（EPR）effect.Furthermore,our drug carrier shows superior therapeutic outcomes compared with the clinically approved SN38 prodrug CPT-11 in the Bcap-37 mouse model of breast cancer.The prodrug-loaded PEGylated UCNPs are also successfully employed in UCL imaging in vitro and ex vivo tissues,showing their excellent biocompatibility and potential as a theranostic scaffold for simultaneous drug delivery and tumor imaging within a single platform.In chapter 4,we undertake an attempt to design a nanosensor for the detection of melamine based on fluorescence resonance energy transfer（FRET）between UCNPs and Graphene oxide（GO）.This part of work is still in progress,and more attention will be payed to the improvement of sensitivity and the detection range,as well as further detection in real samples.In chapter 5,we summarize the present work and point out the deficiency of this thesis,and future prospects and efforts towards this work are also envisioned.