Abstract
Upconversion nanoparticles (UCNPs)-based photodynamic nanotheranostic agents could address the main drawbacks of photosensitizer molecules (PSs) including instability in aqueous solution and rapid clearance. Due to the relatively weak luminescence intensity of UCNPs and insufficient reactive oxygen species (ROSs), UCNPs-based photodynamic therapy (UCNPs-PDT) was discounted for deep-seated tumors. Thus, we proposed a PSs-modulated sensitizing switch strategy. Indocyanine green (ICG) as an NIR organic dye was proved to effectively enhance the luminescence intensity of UCNPs. Herein, four-color UCNPs were coated with a silica layer which loaded ICG and PSs while the thickness of silica layer was controlled to assist the sensitization function of ICG and activation of PSs. Under the drive of mitochondria-targeting ligand, the prepared nanotheranostic agent would accumulate in the mitochondria where ROSs were in-situ produced and then cell apoptosis was induced. Due to the cooperative PDT and high tissue-penetration depth of NIR laser, the prepared upconversion nanotheranostic agent could achieve significant inhibition on the deep-seated tumors.
Highlights
As an exogenous stimulus for activatable theranostics, light presents the advantages of high spatiotemporal selectivity and negligible side effects, and has been widely applied for photothermal, photodynamic, and/or photo-triggered chemo/gene therapy (Huang et al, 2014)
The prepared Upconversion nanoparticles (UCNPs)@SiO2/HA/MB/Indocyanine green (ICG) nanoprobe was coated with PEG-NH2 via the silanization reaction and the mitochondria recognition ligand, TPP, was further attached through the carbodiimide reaction to obtain the final nanotheranostic agent, UCNPs@SiO2/HA/MB/ICG@PEGTPP (Liu et al, 2014)
The Zeta-potential of the UCNPs nanoprobe became positive when coated with PEG-NH2 (Figures 2B,C), and the mitochondria-targeting ligand, TPP, could further increase the Zeta-potential of the nanoprobe, which could benefit their accumulation in the mitochondria (Figure 2D)
Summary
As an exogenous stimulus for activatable theranostics, light presents the advantages of high spatiotemporal selectivity and negligible side effects, and has been widely applied for photothermal, photodynamic, and/or photo-triggered chemo/gene therapy (Huang et al, 2014). Photodynamic therapy (PDT) use photosensitizers (PS) to produce reactive oxygen species (ROSs) which could selectively and irreversibly destroy cancer cells and tumor tissue without damaging adjacent healthy ones. UCNPs have the obvious merits of high tissue-penetration depth, negligible auto-fluorescence background, and low biotoxicity (Liu Y. et al, 2016). Under the excitation of NIR, UCNPs as the energy donor could effectively excite PS molecules (energy acceptor) to perform PDT via the luminescence resonance energy transfer (LRET) strategy (Fan et al, 2014; Liu et al, 2015; Chen et al, 2017). UCNPs-based PDT efficacy is discounted, especially for the deep-seated malignant tumors
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