NIR-IIb light-triggered upconversion nanoparticles for tumors photodynamic therapy

Abstract

Recently the fluorescence imaging in the second near-infrared biological window b (NIR-IIb 1500–1700 nm) has emerged as a promising strategy owing to high resolution and deeper tissue penetration However in marked contrast to the rapid development in the bioimaging field hitherto no concrete study has been directed toward photodynamic therapy (PDT) therapeutic design following NIR-IIb region excitation Therefore the present study aims to design a 1550 nm (located in NIR-IIb window) light-responsive upconversion nanoparticles (UCNPs) to establish dual-PDT and applications to treat pancreatic tumors Chapter 1 provides an overview of PDT and its Achille’s heel NIR-IIb biological window UCNPs the dual functions of Er3+ ion the concept of UCNPs-based PDT and dual photosensitizer loading strategy The NIR-IIb window's advantages including near-zero autofluorescence low light scattering and deep tissue penetration were highlighted Besides Er3+ ions can serve dual functions as activator and sensitizer are the great instinct enabling harvest the energy of 1550 nm excitation for effective upconversion process The enhanced singlet oxygen (1O2) generation in dual-PDT applications also was introduced The detailed experimental procedures were further shown in Chapter 2 Chapter 3 presents the main finding of this study The core-shell structure of LiYbF4:30%Er@LiGdF4 (shell thickness of 8 4 nm) UCNPs was synthesized which can be excited by a 1550 nm (NIR-IIb) laser Then the dual-photosensitizers (PSs) rose bengal (RB) and chlorin e6 (Ce6) were carried by the silica-coated core-shell LiYbF4:Er@LiGdF4 UCNPs via electrostatic attraction and covalently bonding respectively forming LiYbF4:Er@LiGdF4@SiO2/RB Ce6 The UCNP's emission in both the green (～548 nm) and red (～666 nm) colors under 1550 nm laser excitation was fully utilized to simultaneously trigger RB and Ce6 respectively Notably the simultaneous activation of dual-PS generated abundant singlet oxygen (1O2) by 1550 nm laser irradiation The water absorption around 1400–1500 nm which may cause a heating-up effect was overcome by performant a laser on-off switching sequence instead of continuous irradiation By comparing the laser energy attenuation after penetration through various pork tissue thicknesses as well as the attenuation coefficient we confirmed the deeper tissue penetration of 1550 nm laser over that of 808 nm laser Subsequently the in vitro experiments including MTT assay live/dead cell staining and confocal imaging demonstrated a synergistic effect with higher PDT efficacy from dual-PS than the single-PS-loaded nanocarriers under a single dose treatment The outcome from in vivo treatment of pancreatic tumors also was consistent with in vitro results showing an enhanced antitumor effect of dual-PDT relative to single-PDT

Date of Award	2021
Original language	English
Supervisor	Chen-Sheng Yeh (Supervisor)