The
low-efficiency cellular uptake property of current nanoparticles
greatly restricts their application in the biomedical field. Herein,
we demonstrate that novel virus-like mesoporous silica nanoparticles
can easily be synthesized, showing greatly superior cellular uptake
property. The unique virus-like mesoporous silica nanoparticles with
a spiky tubular rough surface have been successfully synthesized
via a novel single-micelle epitaxial growth approach in a low-concentration-surfactant
oil/water biphase system. The virus-like nanoparticles’ rough
surface morphology results mainly from the mesoporous silica nanotubes
spontaneously grown via an epitaxial growth process. The obtained
nanoparticles show uniform particle size and excellent monodispersity.
The structural parameters of the nanoparticles can be well tuned with
controllable core diameter (∼60–160 nm), tubular length
(∼6–70 nm), and outer diameter (∼6–10
nm). Thanks to the biomimetic morphology, the virus-like nanoparticles
show greatly superior cellular uptake property (invading living cells
in large quantities within few minutes, <5 min), unique internalization
pathways, and extended blood circulation duration (t1/2 = 2.16 h), which is much longer than that of conventional
mesoporous silica nanoparticles (0.45 h). Furthermore, our epitaxial
growth strategy can be applied to fabricate various virus-like mesoporous
core–shell structures, paving the way toward designed synthesis
of virus-like nanocomposites for biomedicine applications.
Inducing
autophagy of macrophages to improve abnormal lipid metabolism
is an important way to treat atherosclerosis (AS). Yet, the current
application of the mammalian target of rapamycin (mTOR)-dependent
autophagy inducers is limited by the side effects and lack of targeting
and low biological availability. Herein, a kind of nitric oxide (NO)-driven
carrier-free nanomotor based on the reaction between trehalose (Tr,
one of the mTOR-independent autophagy inducers), L-arginine (Arg), and phosphatidylserine (PS) is reported. The developed
nanomotors use NO as the driving force, which is generated from the
reaction between Arg and excessive reactive oxygen species (ROS) and
inducible nitric oxide synthase (iNOS) specifically presenting in
the AS microenvironment. The high expression of ROS and iNOS in the
AS site can be used as chemoattractants to induce chemotaxis behavior
of the nanomotors to achieve the first-step targeting an AS plaque.
Subsequently, the “eat me” signal sent by PS is exploited
to precisely target to the macrophages in the AS plaque, realizing
the plaque-macrophage-targeted effect by this step-by-step strategy. In vitro and in vivo results confirm that
the introduction of the concept of carrier-free nanomotors has greatly
improved the biological availability of trehalose (the dose can be
reduced from 2.5 g kg–1 in previous reports to 0.01
g kg–1 in this work). Particularly, consumed ROS
and the production of NO during the targeting process also play positive
roles, in which the former regulates the M2 polarization of macrophages
and the latter promotes the reconstruction of an endothelial barrier,
which contributes to the multilink treatment of AS.
One
of the difficulties in atherosclerosis treatment is that the
ablation of inflammatory macrophages, repair of vascular endothelial
injury, and anti-tissue proliferation should be considered. However,
there are few studies that can solve the abovementioned problems simultaneously.
Herein, we present a kind of near-infrared (NIR) light-driven multifunctional
mesoporous/macroporous tubular micromotor which can rapidly target
the damaged blood vessels and release different drugs. Their motion
effect can promote themselves to penetrate into the plaque site, and
the generated heat effect caused by NIR irradiation can realize the
photothermal ablation of inflammatory macrophages. Furthermore, these
micromotors can rapidly release the vascular endothelial growth factor
for endothelialization and slowly release paclitaxel for antiproliferation
to achieve synergistic treatment of atherosclerosis. In vivo results demonstrated that the micromotors can achieve a good therapeutic
effect for atherosclerosis. This kind of micro/nanomotor technology
with a complex porous structure for drug loading will bring a more
potential treatment platform for the disease.
Drug‐coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug‐loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA‐TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA‐TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug‐loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti‐AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.
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