Mechanised lubricating silica nanoparticles for on-command cargo release on simulated surfaces of joint cavities

Article abstract of DOI:10.1039/c8cc10069a

We describe a type of supramolecular host-guest function silica nanoparticle activated by energy conversion from joint movement. The high coefficient of friction from damaged joints causes more energy conversion, weakening the surface host-guest interaction and resulting in target cargo release. Additionally, the hydrated layer on the nanoparticle surface plays a role in lubrication enhancement.

Full text of DOI:10.1039/c8cc10069a

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DOI: 10.1039/C8CC10069A
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Mechanised Lubricating Silica Nanoparticles for On-Command
Cargo Release on Simulated Surface of Joint Cavity
Xiaolong Tan,†a Yulong Sun,†a Tao Sun a and Hongyu Zhang *a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
We describe a type of supramolecular host-guest functioned silica activation could not be applied in joint cavity.24, 25 Therefore,
nanoparticles activated by energy conversion from the joint herein we propose a release system, combining the properties
movement. High coefficient of friction from damaged joints causes of the cartilage tissues. In this design, we use the heat energy,
more energy conversion to weaken the surface host-guest which is converted from the movement of joints. The increase
interaction, resulting in target cargo release. Additionally, the in temperature can lower the binding constant of the surface
hydrated layer on the nanoparticle surface plays a role in inclusion complex.26 Thereby the design can be stimulated to
lubrication enhancement.
release the drug locally. More importantly, the damage to the
surface of the joint cavity, like osteoarthritis, leads to an
increase of coefficient of friction (COF). Therefore, in the
pathological joint movement, more mechanical energy will
convert to heat, which results in a significant rise in drug
release. At the same time, highly charged molecules are
assembled on the surface of the nanoparticles, which form
hydration layers, thus improving the lubrication property.27 The
local release of anti-inflammatory drug and lubrication
enhancement are both desired for osteoarthritis treatment.
Mechanised silica nanoparticles (MSNs) have been paid much
attention in the last two decades.1 Three significant elements
are involved in these systems, including (i) porous materials, like
mesoporous silica nanoparticles,2 as nanocontainers; (ii)
switchable interlocked molecules (SIM) as stoppers such as
rotaxanes and pseudorotaxanes;3,4 and (iii) extra activation
methods such as light,5-7 pH value,8-12 heat,12-14 reduce-oxide,15
and enzyme16 activations. To achieve the purposes of controlled
release, SIMs are installed on the surface of MSNs, which will
generate the nanoscale movement in the suitable activations. The fabrication activation approaches of the MSNs are depicted
The first MSNs was raised in 2004,17 which showed the in Fig. 1 and ESI. Betaines (chemical structure in Fig. 1) are
effectively controlled release properties of organic dye. installed on the surface of aminated silica nanoparticles (MSNs-
However, the performance of release has been limited as it
could only work in an organic solvent. From 2007, the design of
the surface SIMs has been replaced by water-soluble
macrocycles, such as cyclodextrin and cucurbituril.18-21 The
release properties in water showed the potential of biological
controlled release. In 2012, a light-activated MSNs was
prepared and performed in biological media, which raised the
meaning of targeting release.7 In the last several years, different
kinds of activation methods and loading containers have been
used and made a good stage on the detection and treatment of
cancer and other diseases.22, 23 However, the cartilage structure
of the joint cavity tends to be relatively closed, the common
a.State Key Laboratory of Tribology, Department of Mechanical Engineering,
Tsinghua University, Beijing 100084, P. R. China.
† These authors contributed equally to this work.
Fig.1 Illustration of friction-controlled mechanized drug delivery
Electronic Supplementary Information (ESI) available: materials preparation and
characterisations, tribological test, controlled release experiments, simulations, and
in vitro cytotoxicity. See DOI: 10.1039/x0xx00000x
system. Two types of activations, (a) dynamic friction, (b)
competitive binding, are applied in this system.
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DOI: 10.1039/C8CC10069A
Fig. 3 The aqueous lubrication properties of bMSNs⊃SC[4]A
(blue) compared with bMSNs (red) by using UMT: (a) COF-time
plots (reciprocating frequency: 2 Hz; applied load: 3 N;
concentration: 1.0 mg/mL); (b) comparison of the COF under
different reciprocating frequencies (concentration: 0.5 mg/mL;
applied load: 1N); (c) comparison of the COF under different
reciprocating loads (concentration: 0.5 mg/mL; reciprocating
Fig.2 Morphological, thermodynamic, and spectroscopic frequency: 5 Hz); (d) comparison of the COF at different
characterisations of bMSNs SC[4]A, compared with MSNs-NH2 concentrations of materials (applied load: 1 N; reciprocating
⊃
and bMSNs: TEM images of (a) bMSNs (distribution of diameter frequency: 5 Hz).
size in the bottom left corner and zeta potential in the top right
There is no visible difference in size, which proves the
modification approach does not destroy the structure of the
materials. Additionally, the size distributions from dynamic light
scattering (DLS) increase because of the formation of hydrated
layers, which is displayed in ESI. The mesostructures of MSNs
are carried out by using BET (Fig. 2c). Combining with the
ordered uniform pores from TEM, we confirm all the MSNs we
use is MCM-41 type.2 More details of pore size distribution by
three methods are tested and calculated in Fig. 2c and ESI. TGA
curves (Fig. 2d) display the increase of weight loss proving the
corner) and (b) bMSNs⊃SC[4]A (distribution of diameter size in
the bottom left corner and zeta potential in the top right
corner); (c) N2 adsorption−desorption isotherm (pore size
distribution in the top left corner) of MSNs-NH2 (black), bMSNs
(red), and bMSNs
(black), bMSNs (red), and bMSNs
⊃
SC[4]A (blue); (d) TGA curves of MSNs-NH2
SC[4]A (blue); (e) FT-IR
⊃
spectra of MSNs-NH2 (black), bMSNs (red), and bMSNs
(blue); (f) XPS spectra of bMSNs (red) and bMSNs
(blue).
⊃
SC[4]A
SC[4]A
⊃
NH2). After loading model cargoes, Rhodamine B (RhB), p- successful preparations of both betaine modification and
sulfonato-calix[4]arenes (SC[4]A) self-assembles with betaines- SC[4]A self-assembly on the surface of MSNs. From FT-IR
modified MSNs (bMSNs) to form the host-guest complex spectra (Fig. 2e),
(Binding Constant: log K = 4.9 )28 and control the loaded cargoes corresponding to the C=O stretching vibration of amides,
out of the nanocontainers (bMSNs SC[4]A@RhB). The indicates betaine molecules have been modified on the surface
a
new peak formed at 1634 cm-1,
⊃
controlled cargo release is achieved by dynamic friction and of MSNs-NH2. The self-assembly step does not form any new
competitive binding. Compared with other activations, dynamic chemical bonds. However, we observe the benzene-based
friction with coherent and periodic process simulates the skeleton vibration from SC[4]A, which is located at 1458 cm−1.
motion of bone joints, which provides a huge contribution to Further evidence of self-assembly in Fig. 2f is provided by using
the drug delivery of joint cartilage structure. Besides, SC[4]A X-ray photoelectron spectra (XPS) due to the new peak
introduces a large number of charges which can assist a belonging to SC[4]A (More detailed discussion of this section is
tenacious hydration layer to reduce the friction and wear of shown in ESI).
bone joints and enhance the lubricating properties of the
The lubrication properties of both bMSNs and bMSNs⊃SC[4]A
surface. Most importantly, we investigate the mechanism of
friction-controlled release and propose the potential lubrication
mechanism, which offers an important basis for further designs.
are evaluated by using Universal Micro-Tribology (UMT) in Fig.
3. Overall, the COF is reduced after the assembly of SC[4]As to
the surface of bMSNs. Fig. 3a shows a high-intensity continuous
Morphological, thermodynamic, and spectroscopic characteri- friction experiment to investigate the total friction properties.
sations of bMSNs SC[4]A, compared with MSNs-NH2 and The friction curve of bMSNs SC[4]A is much smoother than
bMSNs, are shown in Fig. 2. TEM images (Fig. 2a and 2b) show before assembly of SC[4]As, which shows the stable lubricating
the sizes before and after modification are around 100 nm. properties of bMSNs SC[4]A. According to the hydration
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sliding frequency. Therefore, different conditions are employed
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DOI: 10.1039/C8CC10069A
to investigate the cargo release property under different loads
(Fig. 4b) and sliding frequencies (Fig. 4c). The cargo release
profiles with no dynamic friction and load of 1 N show a similar
tendency, only a limited cargo (less than 20%) is released after
120 min. Nevertheless, bMSNs⊃SC[4]A@RhB are effectively
activated under the load of 4 N, with a total cargo release
reaching 50% after 120 min. It indicates that the host-guest
interaction between SC[4]A and betaine could not be weakened
under mild load (1 N). But under serve friction (4 N), the
increase of temperature leads to the destruction of the host-
guest interaction, resulting in an obvious cargo release.
Apparently, the higher the sliding frequency is, the faster the
temperature accumulates and the quicker the cargo releases. In
addition, the cargo release properties of bMSNs@RhB and
Fig. 4 Controlled release profiles of bMSNs⊃SC[4]A@RhB: (a)
bMSNs⊃SC[4]A@RhB with a competitive binding agent is
numerical simulation of energy conversion by ABAQUS
including temperature distribution curve of the distance from
the contact area (upper) and temperature distribution of center
longitudinal section of the simulated movement surface
performed by adding ethylenediamine (Fig. 4d). Compared with
the competitive binding approach, the release performance of
dynamic friction is much gentler and more controllable, thereby
enhancing the efficiency and availability of loading cargoes.
(lower); (b) release curves of bMSNs
dynamic friction of different loads: 0 N (pink), 1 N (wine) and 4
N (navy); (C) release curves of bMSNs SC[4]A@RhB with 4 N
⊃SC[4]A@RhB with 2 Hz
In conclusion, the smart release system, bMSNs⊃SC[4]A, is
⊃
successfully applied and activated by the movement of
simulated bone joints. The inclusion complexes on the surface
not only control the release of the cargoes but also reduce the
friction and wear of the joint surface. The mechanism of release
is mainly due to the conversion of mechanical energy into heat
during the friction process. The hydrated lubrication layer
formed by the highly charged structure of the surface
significantly reduces the COF, thereby improving the friction
and wear properties of the surface. As the friction conditions
changed, the COF does not change significantly, and the
lubrication mechanism conforms to boundary lubrication. In
addition, we have made appropriate evaluations on the toxicity
loaded dynamic friction of different frequencies: 1 Hz (green), 2
Hz (navy), and 3 Hz (purple); (d) release curves of competitive
binding (binding agent: 2 mL ethylenediamine, blue), compared
with the release curve of bMSNs@RhB (red) and
bMSNs⊃SC[4]A@RhB without any activation (pink).
lubrication mechanism,27 SC[4]A molecules attract more
charges onto the surface of bMSNs to form a tenacious
hydrated layer, which improves the lubrication performance. To
further determine the lubrication mechanism of bMSNs and
bMSNs⊃SC[4]A, we also test the COFs with different
frequencies, loads, and concentrations. Generally, there is only
a slight difference among various conditions, especially the
tests in frequencies and loads. Although we discover a relatively
apparent increasing of COF with different concentrations, it is
related with the abrasive effect of MSNs.25 Therefore, we
propose the lubrication mechanism of this system is boundary
lubrication according to the Stribeck curve (More details about
lubrication states are shown in ESI).
and biocompatibility of bMSNs⊃SC[4]A (More details in ESI),
thus demonstrating the biological application prospects of the
smart release system in the future.
This study is financially supported by National Natural Science
Foundation of China (Grant no. 51675296), Ng Teng Fong
Charitable Foundation (Grant No. 202-276-132-13), Tsinghua
University Initiative Scientific Research Program (Grant no.
20151080366), and Research Fund of State Key Laboratory of
Tribology, Tsinghua University, China (Grant no. SKLT2018B08).
The release profiles and mechanism of bMSNs⊃SC[4]A@RhB
with dynamic friction are examined, compared with the release
of competitive binding (Fig. 4). The energy conversion during
dynamic friction between the surfaces of the joint cavity is
simulated and shown in Fig. 4a. Parts of the generated
mechanical energy converted into heat, which leads to a
significant increase in temperature at the contact area. After a
reciprocating movement of 4.5 s, local temperature at contact
area raises to 50.79 oC (More details in ESI). Due to the increase
in contact temperature, a significant entropy increase occurs on
the surface of the material. The mounting surface chaos directly
impairs the ion-dipole interaction of the inclusion complex,26
thereby releasing the molecules out of the inorganic container.
The speed of the generation of energy, corresponding to the
accumulation of temperature, depends mainly on the load and
Conflicts of interest
There are no conflicts to declare.
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