Research ArticleAPPLIED SCIENCES AND ENGINEERING

Nanoparticle elasticity regulates phagocytosis and cancer cell uptake

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Science Advances  17 Apr 2020:
Vol. 6, no. 16, eaaz4316
DOI: 10.1126/sciadv.aaz4316
  • Fig. 1 Synthesis and characterization of SNCs.

    (A) Schematic illustration of the synthesis of SNCs having controllable Young’s moduli. (B) TEM micrographs (scale bars, 200 nm) and (C) AFM height profiles (scale bars, 500 nm) of SNCs. (D) SEM micrographs (scale bars, 200 nm) of SNCs synthesized using 0% (softest) and 100% (stiffest) of TEOS. (E) Young’s moduli of SNCs (values are means ± SD, n = 15).

  • Fig. 2 Effects of SNC elasticity on cellular interactions.

    (A) Schematic illustration showing different types of cell-SNC interactions. (B) The uptake of the softest and the stiffest SNCs by RAW264.7 and SKOV3 cells; inset is the magnified graph of the first two groups. (C) The cellular uptake and binding of SNCs were measured at 4° and 37°C, respectively. (D) Four-hour cellular uptake and binding of FA-PEG–modified SNCs in RAW264.7 and (E) SKOV3 cells; values are compared to the SNCs having the highest Young’s modulus. (F) Four-, 12-, and 24-hour cellular uptake of FA-PEG–modified SNCs in RAW264.7 and (G) SKOV3 cells; at every time point, values are compared to the SNCs having the highest Young’s modulus. All values are means ± SD (n = 3, with *P < 0.05, **P < 0.01, and #P < 0.001; N.S., not significant).

  • Fig. 3 Endocytic pathways and deformations of SNCs during cellular uptake.

    (A) Uptake ratios of the FA-PEG–modified SNCs in SKOV3 cells. (B) TEM micrographs showing the morphological change of the stiffest (top) and softest (bottom) SNCs during receptor-mediated interactions with SKOV3 cells. (C) Schematic illustration showing the deformation of the softest SNCs during receptor-mediated cellular uptake. (D) Considerable proportion of SKOV3 cell surface can be covered by a large number of adhered SNCs. (E) Uptake ratios of the FA-PEG–modified SNCs in RAW264.7 cells. (F) TEM micrographs showing the morphological change of the softest SNCs during interactions with RAW264.7 cells. The uptake ratio represents the uptake of SNCs by cells treated with endocytic inhibitors normalized by the uptake by nontreated ones. Scale bars, 200 nm. All values are means ± SD (n = 3, with *P < 0.05, **P < 0.01, and #P < 0.001; N.S., not significant).

  • Fig. 4 The endocytic pathway–dependent deformation of SNCs is a result of the associated proteins.

    (A) Uptake ratios of the PEG-modified softest SNCs in SKOV3 cells. The uptake ratio represents the uptake of SNCs by cells treated with endocytic inhibitors normalized by the uptake by nontreated ones. (B) TEM micrographs showing the morphological change of the softest PEG-modified SNCs during interactions with SKOV3 cells; scale bars, 200 nm. (C) Schematic illustration showing the proteins associated in the three types of SNC-cell interactions. All values are means ± SD (n = 3).

  • Fig. 5 The internalization kinetics of the softest (0% TEOS, 560 kPa) and the stiffest (100% TEOS, 1.18 GPa) SNCs in receptor-mediated uptake by SKOV3 cells.

    (A) Fluorescence live-cell images showing the internalization of the softest and (B) stiffest FA-PEG–modified SNCs by SKOV3 cells and their transport to lysosomes over 60 min; scale bars, 20 μm. Representative time projection images showing the movement of the (C) softest and (D) stiffest SNCs during cellular uptake; tracks of the SNCs are shown in the magnified images of boxed regions. Yellow solid lines indicate the plasma membranes; scale bars, 10 μm. Instantaneous velocity of the (E) softest and (F) stiffest SNCs during stage I and stage II of cellular uptake. MSD analysis of the movement of the (G) softest and (H) stiffest SNCs during stage I and stage II of cellular uptake; insets are magnified graphs. (I) Time taken for the internalization of SNCs. Movements of the SNCs were only recorded for 15 min, as imaging longer than 15 min could lead to fluorescence quenching and focal plane shifting.

  • Table 1 Hydrodynamic size, PDI, ζ potential, Young’s modulus, and surface PEG density of FA-PEG–modified SNCs.

    Values are means (n = 3) for hydrodynamic diameter, PDI, ζ potential, and Young’s modulus. Coating of FA-PEG–modified SNCs consists of 10% FA-PEG and 90% mPEG (in molar ratio).

    Molar percentage
    of TEOS
    05102040100
    Hydrodynamic
    diameter (nm)
    202203202205206211
    PDI0.120.120.110.070.090.09
    ζ potential (mV)−3.5−3.1−3.5−3.3−3.2−2.8
    Young’s modulus
    (MPa)
    0.5625.09108.53224.71459.431184.46
    Surface PEG density
    (molecules/nm2)
    0.940.830.820.880.960.89

Supplementary Materials

  • Supplementary Materials

    Nanoparticle elasticity regulates phagocytosis and cancer cell uptake

    Yue Hui, Xin Yi, David Wibowo, Guangze Yang, Anton P. J. Middelberg, Huajian Gao, Chun-Xia Zhao

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