Fabrication Of Targetable Upconversion Nanoparticles For Biosensing, Multimodle Imaging And Tumor Therapy

Nanoparticles-based imaging probes and drug delivery systems have been applied in bioimaging and tumor therapy. Upconversion nanoparticles (UCNPs), due to its unique optical properties excited by continuous-wave near-infrared (NIR) light to transfer to higher energy photoluminescence, remarkable photo-and chemical-stability, nonblinking emission and narrow emissions, make them attractive to fabricate theranostic probes for bioimaging and biodetection due to auto-fluorescence removal and large penetration depth. The targetability of a theranostic probe plays a key role to assuring its theranostic efficiency. However, further development of UCNPs in bioapplication is hindered due to few targeting stragety available for UCNPs. This dissertation is to develop the present targeting stragety, to fabricate UCNP-based theranostic probe intergated with tumor-targeted sensing, imaging and therapy, and to exploit dual-targeting strategy to promote tumor-targeted specificity and therapy effiency of UCNPs. It is expected that the research results of this dissertation will be potentially helpful for early diseases diagnosis as well as therapy in cancer development.(1) Bionanoparticles and nanostructures with high biocompatibility and stability, low toxicity, diversification of imaging modality and specificity of targeting to desired organs or cells are of great interest in nanobiology and medicine. However, integrating all of these desired features into a single bionanoparticle, which can be applied to biomedical applications and eventually in clinical prediagnosis and therapy, is still a challenge. We herein report a facile one-step solvothermal approach to fabricate targetable and biocompatible β-NaYF4:Yb,Gd,Tm upconversion nanoparticles (UCNPs) with bimodal-signals (near infrared (NIR) fluorescence and magnetic resonance (MR) signals) using hyaluronic acid (HA) as a multifunctional molecule. The prepared UCNPs with low toxicity are successfully applied for in vitro and in vivo targeted tumor imaging. The developed biomimetic surface modification approach for the synthesis of biomolecule-guided multifunctional UCNPs holds great potential applications in medical diagnostics and therapy.(2) A theranostic probe has emerged as a promising tool for cancer therapy and bioimaging enhancement. Herein, we fabricate a theranostic nanoprobe via esterification incorporated10-hydroxycamptothecine (CPT) to hyaluronic acid functionalized UCNPs, exploiting UCNPs as imaging agent, HA as targeting ligand and CPT as the drug reagent. Furthermore, in the base of the interaction of CPT and Topoisomerase I (TOPO I), CPT-HA-UCNPs (donors) and graphene oxide (GO)(quencher) were employed to fabricate a turn-off fluorescent probe of CPT-HA-UCNPs/GO composite for sensing TOPO I. The proposed nanoprobe integrated sensing, imaging and therapy into one, providing a strategy for the next generation of tumor-targeted UCNPs-based theranostic nanoplatform.(3) The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of1O2due to multiplexed Forster resonance energy transfer between APBA-UCNPs (donor) and HAC60(acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.