Enhanced Red Upconversion Emission of NaYF₄:Yb³⁺, Er³⁺, Mn²⁺ Nanoparticles for Near-infrared-induced Photodynamic Therapy and Fluorescence Imaging

Abstract

Polyethyleneimine (PEI)-capped NaYF 4 nanoparticles (NPs) codoped with Yb 3+ , Er 3+ , and Mn 2+ ions (MnUNPs) were synthesized via a solvothermal method. The MnUNPs showed tissue-penetrable over-1000 nm (OTN-) near-infrared (NIR) and strong red upconversion (UC) emission under NIR excitation. Furthermore, the photosensitizers chlorin e6 (Ce6) and biocompatible poly(ethylene glycol) (PEG) were immobilized on the surface of the MnUNPs (PEG/Ce6-MnUNPs). The prepared PEG/Ce6-MnUNPs generated singlet oxygen ( 1 O 2 ) and displayed effective anticancer activity under NIR excitation. Keywords: Photodynamic therapy | Second biological window | UpconversionPhotodynamic therapy (PDT) is a technique that destroys cancer tissues via photosensitizers and light irradiation.1,2 The photosensitizers absorb the light and produce reactive oxygen species (ROS) that destroy cancer cells. Most current photosensitizers require visible (vis) light for excitation, and their use in cancer treatment suffers from the lack of penetration depth of vis light owing to the scattering it undergoes because of its short wavelength.Because of this drawback of PDT, rare-earth-doped ceramic nanophosphors (RED-CNPs) have attracted much attention as in vivo imaging probes 35 and PDT transducers. 69 The RED-CNPs produce simultaneous tissue-penetrable over-1000 nm near-infrared (OTN-NIR) and vis upconversion (UC) emission under NIR excitation. , Er 3+ NP) showed green and red UC emission under 980-nm NIR excitation and was used as a transducer for PDT. In those studies, the photosensitizer, chlorin e6 (Ce6) ( Figure S1 in Supporting Information (SI)) was immobilized on the surface of the , Mn 2+ NPs (MnUNPs) for the transducer of PDT using a standard solvothermal synthesis method. Ce6 was covalently immobilized on the surface of the polyamine-tethered NPs via amide linkage. Furthermore, for a highly stable PDT probe, the biocompatible polymer poly(ethylene glycol)-blockpoly(acrylic acid) (PEG-b-PAAc) was strongly immobilized on the positive-charged polyamine surface of the NPs via electrostatic interactions (Figure 1).The MnUNPs were synthesized using the solvothermal synthesis method with different nominal Mn 2+ concentrations (4054 mol %)1518 and a fixed concentration of water (4 wt %), as in previous literature. As a control, Mn 2+ -undoped NaYF 4 :Yb 3+ , Er 3+ NPs (UNPs) were also synthesized using the same protocol. X-ray diffraction (XRD) spectroscopy identified the crystal phase of the synthesized MnUNP samples to be pure cubic α-phase NaYF 4 , because all the peaks were indexed to JCPDS data (06- Figure 1. Illustration of NIR-induced PDT and OTN-NIR fluorescence imaging based on PEG/Ce6-MnUNPs.

Temperature Sensing of Deep Abdominal Region in Mice by Using Over-1000 nm Near-Infrared Luminescence of Rare-Earth-Doped NaYF4 Nanothermometer

“…Nanotechnology has offered investigators novel materials and tools against challenging problems that have remained unresolved for decades. Indeed, nanotechnology has allowed in vivo deep tissue imaging 1 – 3 , single photon emission tomography (SPECT)/computed tomography (CT) in vivo dual-modal imaging 4 , safe and controlled drug delivery 5 , and near-infrared (NIR)-induced photodynamic therapy 6 . In addition, nanotechnology has also enabled thermal therapy techniques such as photothermal therapy (PTT) 7 – 9 , making preeminent contributions to clinical studies.…”

Oxygen Self-Sufficient Amphiphilic Polypeptide Nanoparticles Encapsulating BODIPY for Potential Near Infrared Imaging-guided Photodynamic Therapy at Low Energy

“…To solve this problem, a variety of nanomaterials (liposomes, polymers, quantum dots, metallic nanostructures, etc.) have been designed, 8 - 11 among which amphiphilic polymer nanoparticles have been proved effective in protecting PSs from water invasion. 12 - 14 Besides, the well-designed compositions, sizes, morphologies make polymer-PS NPs easily accumulate in the tumor tissue through enhanced permeability and retention (EPR) effect, and then present effective PDT under light irradiation.…”

Lanthanide-doped near-infrared II luminescent nanoprobes for bioapplications

“…NaYF 4 :Yb/Er [46], NaCeF 4 :Er/Yb@NaCeF 4 [57], NaYF 4 :Yb/Er/Mn [103], to name a few. In one pioneering work, Naczynski et al [46] demonstrated the application of NaYF 4 :Yb/Er NPs for in vivo NIR-II bioimaging upon excitation at 980 nm ( Fig.…”