Bismuth Ferrite Second Harmonic Nanoparticles for Pulmonary Macrophage Tracking

Abstract

utilizing near-infrared NPs. [3] While optical imaging can provide functional information, its main disadvantage is the low penetration depth and high background from tissue autofluorescence. [4] More recently however, second and third harmonic generation (SHG and THG) nanomaterials have been generated that can be efficiently employed in the second near infrared window (NIR-II) [5] using a multiphoton microscope. They have several inherent advantages, i) providing a significantly higher penetration depth; ii) no bleaching or blinking; and iii) emitting both, SHG and THG signals that allow them to be detected regardless of the endogenous background signal emitted by collagen and lipids for example. [6,7] Bismuth ferrite (BiFeO 3 ) harmonic nanoparticles (BFO-HNPs) have excellent SHG and THG capabilities [8] and were recently shown to be highly biocompatible in human cell lines, [9] and can be used for monitoring of human stem cells in depth of skeletal muscle tissue at more than one millimeter from the surface. [6] BFO is the material of choice among all metal-oxides since its nonlinear coefficients is one of the highest, along with its large wavelength excitation range, reaching further into the infrared window. [8] In this work, we demonstrate the possibility of using BFO-HNPs for monitoring pulmonary macrophages. The lung Recently, second harmonic generation (SHG) nanomaterials have been generated that are efficiently employed in the classical (NIR) and extended (NIR-II) near infrared windows using a multiphoton microscope. The aim was to test bismuth ferrite harmonic nanoparticles (BFO-HNPs) for their ability to monitor pulmonary macrophages in mice. BFO-loaded MH-S macro phages are given intratracheally to healthy mice or BFO-HNPs are intranasally instilled in mice with allergic airway inflammation and lung sections of up to 100 μM are prepared. Using a two-photon-laser scanning microscope, it is shown that bright BFO-HNPs signals are detected from superficially localized cells as well as from deep within the lung tissue. BFO-HNPs are identified with an excellent signal-to-noise ratio and virtually no background signal. The SHG from the nanocrystals can be distinguished from the endogenous collagen-derived SHG around the blood vessels and bronchial structures. BFO-HNPs are primarily taken up by M2 alveolar macro phages in vivo. This SHG imaging approach provides novel information about the inter action of macrophages with cells and the extracellular matrix in lung disease as it is capable of visualizing and tracking NP-loaded cells at high resolution in thick tissues with minimal background fluorescence. Second Harmonic NanoparticlesThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Harmonic generation at the nanoscale

“…sub-cellular spatial resolution proper to optical approaches (and not accessible to MRI, CT and other whole body imaging techniques) constitutes an undeniable asset for tracking individual cells, with straightforward applications for the assessment of regenerative therapies based on the engraftment of stem cells [Dubreil et al (2017)] and for studies on immune-response reactions [Ramos-Gomes et al (2019)].…”

Wavelength-Selective Nonlinear Imaging and Photo-Induced Cell Damage by Dielectric Harmonic Nanoparticles

“…Harmonic generation is a parametric nonlinear process where N incident photons at frequency ω interacting with a nonlinear medium are scattered as a single photon at frequency N × ω. As we previously demonstrated, the co-localization of SHG and THG typically excited between 1200-1300 nm leads to additional selectivity against background, in fact it can be exploited to detect HNP-labelled structures against endogenous sources of harmonic signals, 2,3 such as collagen or lipids. 4 Furthermore, the long excitation wavelengths strongly limit autofluorescence that may hinder the marker detection in tissues.…”

“…It was previously shown that BFO HNPs are suitable cell markers for nonlinear microscopy. 2,3 Their contrast is based on second-and third-harmonic generation (SHG, THG) rather than luminescence. Harmonic generation is a parametric nonlinear process where N incident photons at frequency ω interacting with a nonlinear medium are scattered as a single photon at frequency N × ω.…”

Resource‐Efficient Low‐Temperature Synthesis of Microcrystalline Pb2B5O9X (X = Cl, Br) for Surfaces Studies by Optical Second Harmonic Generation

“…Among all the tools developed for surfaces analysis over the years (e.g., electron scattering and diffraction, photoemission, and mass spectroscopy), SHG receives much attention due to its nondestructive measurement principle and wide applicability. [ 3,8–11 ] For example, SHG does not require ultrahigh vacuum like electron scattering and diffraction, photoemission, and mass spectroscopy. However, SHG technique may not have enough surface specificity and sensitivity if the signal contributed by the bulk cannot be suppressed.…”