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Super‐Resolution Mapping of Single Nanoparticles inside Tumor Spheroids
Author(s) -
Liu Yongtao,
Wang Fan,
Lu Hongxu,
Fang Guocheng,
Wen Shihui,
Chen Chaohao,
Shan Xuchen,
Xu Xiaoxue,
Zhang Lin,
Stenzel Martina,
Jin Dayong
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201905572
Subject(s) - spheroid , nanoparticle , materials science , resolution (logic) , excitation , scattering , excitation wavelength , bessel beam , laser , optics , microscopy , optoelectronics , nanotechnology , wavelength , beam (structure) , chemistry , in vitro , physics , computer science , biochemistry , quantum mechanics , artificial intelligence
Cancer spheroids have structural, functional, and physiological similarities to the tumor, and have become a low‐cost in vitro model to study the physiological responses of single cells and therapeutic efficacy of drugs. However, the tiny spheroid, made of a cluster of high‐density cells, is highly scattering and absorptive, which prevents light microscopy techniques to reach the depth inside spheroids with high resolution. Here, a method is reported for super‐resolution mapping of single nanoparticles inside a spheroid. It first takes advantage of the self‐healing property of a “nondiffractive” doughnut‐shaped Bessel beam from a 980 nm diode laser as the excitation, and further employs the nonlinear response of the 800 nm emission from upconversion nanoparticles, so that both excitation and emission at the near‐infrared can experience minimal loss through the spheroid. These strategies lead to the development of a new nanoscopy modality with a resolution of 37 nm, 1/26th of the excitation wavelength. This method enables mapping of single nanoparticles located 55 µm inside a spheroid, with a resolution of 98 nm. It suggests a solution to track single nanoparticles and monitor their release of drugs in 3D multicellar environments.