Abstract
Nanoparticles from magnetotactic bacteria have been used in conventional imaging, drug delivery, and magnetic manipulations. Here, we show that these natural nanoparticles and their bioinspired hybrids with near-infrared gold nanorods and folic acid can serve as molecular high-contrast photoacoustic probes for single-cell diagnostics and as photothermal agents for single-cell therapy using laser-induced vapor nanobubbles and magnetic field as significant signal and therapy amplifiers. These theranostics agents enable the detection and photomechanical killing of triple negative breast cancer cells that are resistant to conventional chemotherapy, with just one or a few low-energy laser pulses. In studies in vivo, we discovered that circulating tumor cells labeled with the nanohybrids generate transient ultrasharp photoacoustic resonances directly in the bloodstream as the basis for new super-resolution photoacoustic flow cytometry in vivo. These properties make natural and bioinspired magnetic nanoparticles promising biocompatible, multimodal, high-contrast, and clinically relevant cellular probes for many in vitro and in vivo biomedical applications.
Highlights
Photoacoustic (PA) methods with fast growing applications in spectroscopy, flow cytometry, microscopy, tomography, and image-guided theranostics offer unique features that other optical modalities cannot, including (1) the ability to assess deep tissue structures, (2) insensitivity to light scattering and autofluorescent backgrounds, and (3) safety and clinical applicability requiring only low laser energy that is within laser safety standards[1,2,3,4,5,6,7,8]
We demonstrated that MBs, natural magnetic nanoparticles (nMNPs), and their bioinspired hybrids with gold nanorods (GNRs) can be used as advanced high contrast and specific agents in PA and PT spectroscopy, cytometry, and flow cytometry in vitro and in vivo for the detection, magnetic manipulation, and therapy of single cells (Fig. 1)
Each PT signal from individual bacteria was a result of averaging thermal effects from intracellular nMNPs, which are naturally packed into magnetosomes inside MBs (Fig. 1)
Summary
Photoacoustic (PA) methods with fast growing applications in spectroscopy, flow cytometry, microscopy, tomography, and image-guided theranostics offer unique features that other optical modalities cannot, including (1) the ability to assess deep (up to 3–5 cm) tissue structures, (2) insensitivity to light scattering and autofluorescent backgrounds, and (3) safety and clinical applicability requiring only low laser energy that is within laser safety standards[1,2,3,4,5,6,7,8]. One of the promising potential biocompatible PA contrast agent is natural magnetic nanoparticles (nMNPs) that are genetically produced in specific organelles (magnetosomes) of magnetotactic bacteria (MBs)[22,23,24,25] These bioproduced nMNPs are single-domain monocrystalline ferrimagnets (magnetite [Fe3O4] or greigite [Fe3S4]) with a high level of purity and crystallinity and a high magnetic moment. MBs and nMNPs are receiving growing interest in biomedical research They have already shown superiority over engineered nanoparticles as (1) contrast agents in magnetic-resonance imaging (MRI); (2) therapeutic agents for magnetic hyperthermia of primary tumors, showing larger magnetic losses when converted into heat; and (3) advanced drug carriers[28,29,30,31,32]. We demonstrated that MBs, nMNPs, and their bioinspired hybrids with gold nanorods (GNRs) can be used as advanced high contrast and specific agents in PA and PT spectroscopy, cytometry, and flow cytometry in vitro and in vivo for the detection, magnetic manipulation, and therapy of single cells (Fig. 1)
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