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On the origin and regulation of ultrasound responsiveness of block copolymer nanoparticles

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  • ReceivedAug 9, 2019
  • AcceptedSep 9, 2019
  • PublishedOct 12, 2019

Abstract


Funding

the National Natural Science Foundation of China(21674081)

Fundamental Research Funds for the Central Universities(22120180109)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21674081) and Fundamental Research Funds for the Central Universities (22120180109).


Interest statement

The authors declare that they have no conflict of interest.


Supplementary data

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Scheme 1

    Illustration of ultrasound responsiveness of block copolymer nanoparticles. Origin: thermodynamic state of nanoparticles. Regulating factors: self-assembly temperature (Ts) and solvents. Ultrasound responsive rate: the higher the Tu, the faster the rate. Vesicles are mainly prepared in THF/water and micelles are mainly prepared in DMF/water, followed by dialysis against water to remove organic solvent (color online).

  • Figure 1

    TEM images of block copolymer nanoparticles after removing organic solvents by dialysis before sonication. Prepared in THF/water and then dialyzed against water: simple vesicles from polymer 1 (a); lamellae from polymer 2 (b); framboidal vesicles from polymer 3 (c); simple vesicles from polymers 4–8 (d–h). Beads-like micelles from polymers 1 and 7, prepared in DMF/water and then dialyzed against water (i, o); complex micelles from polymers 2–6 (j–n); large compound vesicles from polymer 8 (p). Samples were stained by neutral phosphotungstic acid except for (h) and (p). The self-assembly temperature (Ts) is 25 °C. More images with higher resolutions are shown in the Supporting Information online.

  • Scheme 2

    Origin and regulation of ultrasound responsiveness of block copolymer nanoparticles. (1) Vesicles at metastable state I in THF/water when Ts is around Tg, with energy barrier ∆E1, show good ultrasound responsiveness; (2) vesicles at metastable state II in THF/water when Ts is below Tg, with higher energy barrier ∆E2, show poorer ultrasound responsiveness (t2>t1); (3) vesicles at stable states in THF/water when Ts is much higher than the Tg, or solid micelles at stable states in DMF/water, do not respond to ultrasound; (4) raising Tu can enhance the responsive rate (t4<t1) but does not change the thermodynamic state of nanoparticles (still at metastable state I, and ∆E1=∆E4) (color online).

  • Figure 2

    TEM images of vesicles self-assembled from polymer 1 in THF/water: Ts=5 °C before (a) and after (c) sonication, and Ts=45 °C before (b) and after (d) sonication. Samples were stained by neutral phosphotungstic acid.

  • Figure 3

    (a) The amount of free radicals produced by ultrasound irradiation against time; (b) influence of free radicals on the ultrasound responsiveness of polymer 1 vesicles by using methylene blue to capture radicals (Figure S18); (c) ultrasonic cavitation from bubbles; (d) variation of hydrodynamic diameters against time by heat annealing at 45 °C (up to 10 d), and then by sonication (up to180 s); (e) comparison of different ways to a thermodynamically stable state by heat annealing and then sonication (color online).

  • Figure 4

    Regulation of ultrasound responsiveness by Ts (a) and solvent (b, c), and regulation of ultrasound responsive rate by Tu (d). (a) Ts around Tg can afford good or excellent ultrasound-responsive vesicles (THF/water, Tu=25 °C). (b) Simple or framboidal vesicles self-assembled in THF/water can respond to ultrasound when Ts is around Tg (for polymers 1, 3–5), but can not respond when Ts is much above or below Tg (polymers 6–8). (c) Micelles (polymers 1, 3–7) and large compound vesicles (LCVs) (polymer 8) self-assembled in DMF/water do not respond to ultrasound. (d) Raising Tu from 25 to 45 °C can enhance the ultrasound responsive rate of metastable vesicles: slight enhancement for simple or framboidal vesicles from polymers 1, 3 and 4 with good ultrasound responsiveness; much more enhancement for simple vesicles from polymer 5 with poor ultrasound responsiveness; no influence on simple vesicles from polymers 6–8 without ultrasound responsiveness. (e) Regulation of ultrasound responsiveness of simple vesicles self-assembled from polymer 1 at various Ts in THF/water, and regulation of the corresponding responsive rate at different Tu. (f) Lamellae from polymer 1 in DMF/water (a), and beads-like micelles from polymer 2 in THF/water (b); Ts=25 °C.

  • Table 1   Summary of block copolymers and the corresponding morphologies at different self-assembly conditions

    Polymer

    Composition

    Hydrophobic block

    Tg (°C)a)

    Mn (Da)

    Ð

    Morphologies (TEM images in Figure 1)

    THF/H2O

    DMF/H2O

    1

    PEO43-b-PBMA44

    Poly(n-butyl methacrylate)

    22

    2600

    1.12

    Simple vesicles (a)

    Beads-like micelles (i)

    2

    PEO43-b-PBMA90

    Poly(n-butyl methacrylate)

    24

    3800

    1.20

    Lamellae (b)

    Complex micelles (j)

    3

    PEO43-b-PMEMA51

    Poly(methoxyethyl methacrylate)

    −2

    7400

    1.22

    Framboidal vesicles (c)

    Complex micelles (k)

    4

    PEO43-b-PEMA49

    Poly(ethyl methacrylate)

    42

    4300

    1.27

    Simple vesicles (d)

    Complex micelles (l)

    5

    PEO43-b-PMMA40

    Poly(methyl methacrylate)

    76

    3100

    1.27

    Simple vesicles (e)

    Complex micelles (m)

    6

    PEO43-b-PDEA65

    Poly[2-(diethylamino)ethyl methacrylate]

    7

    3500

    1.04

    Simple vesicles (f)

    Complex micelles (n)

    7

    PEO43-b-PtBA77

    Poly(tert-butyl acrylate)

    −1

    5600

    1.09

    Simple vesicles (g)

    Beads-like micelles (o)

    8

    PEO43-b-PS106

    Polystyrene

    96

    4100

    1.11

    Simple vesicles (h)

    Large compound vesicles (p)

    Tg of the hydrophobic segments of block copolymers. The Tg of polymer 3 (−2 °C) is much lower than the theoretical value of its hydrophobic block of PMEMA (22 °C) while the Tg of polymer 7 (−1 °C) is much higher than the theoretical value of its hydrophobic block of PtBA (−22 °C). So their theoretical values are taken into account to support the results of regulation of ultrasound responsiveness by Ts.

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