Upconversion Nanoparticles Featured With NIR Triggered Functional Molecules For Biomedical Applications

With the development of Nanomedicine,optical-triggered releasing systems based on nano materials have been proposed for a wide range of applications,including drug delivery,biological sensing,light-triggered switching,and light-triggered gene expression and cancer therapies.However,UV light as the excitation light of most photosensitizers suffers from a short tissue penetration depth and damage to biological tissue,which somehow limit their applications in the biomedical field.Upconversion nanoparticles(UCNPs)have increasingly become attractive to many researchers because of their unique ability of transforming near-infrared(NIR)light into visible light or UV light.The luminescence spectra of UCNPs depend on the type of rare earth elements doped into the nanoparticles during synthesis.Besides a deeper tissue penetration and lower biological tissue damage featured by the NIR light,the advantages of UCNPs include long luminous life,high photo-stability,adjustable luminescence spectra,and relatively good biocompatibility,thus promising important applications in nanomedicine.This thesis mainly describes my efforts in the development of NIR-triggered molecular releasing system based on UCNPs,including the two parts as follows:Part 1: Application of upconversion nanoparticles in neural regenerative medicine.We have developed multifunctional UCNPs with different surface modification to excite the ion channel proteins.The membrane potential changes produced by stimulating neurons can impact the specific neuronal circuits,allowing the damaged neuron axon to regenerate new connection with the downstream neurons in the spinal cord-injured mouse models.We have verified the neuron regeneration from mouse spinal cord slices and the feeding experiments in vivo.These experiments support that NIR light can trigger the functional molecules assisted by UCNPs according to our design,and implement the application in neuron regenerative medicine in vivo under the imaging guidance.Part 2: Application of tumor vascular microenvironment enhancement based on upconversion nanoparticles.I have developed multi-functional UCNPs containing magnetic components with a core-shell structure for a magnetically targeting drug carrier system.After magnetic enrichment inside the breast cancer tumors in vivo,UCNPs can transform NIR light into UV light which cut off the key chemical bond of a nitric oxide precursor(SNAP)for controllable releasing of gaseous signaling molecules.We have demonstrated that the nitric oxide(NO)released in tumor can effectively improve tumor vascular microenvironment,potentially benefiting the therapeutic effects of chemotherapy and reducing the dosages.In a short summary,I have attempted to systematically investigate near-infrared light induced ion regulation and gaseous signaling molecule releasing controlled by UCNPs-based technologies.My work has demonstrated the great potentials of UCNPs in biomedical research by paving new avenues to address the critical questions in neural regenerative medicine and tumor therapies.