Life
is recognized as a sophisticated self-assembling material
system. Cancer involves the overexpression and improper self-assembly
of proteins, such as cytoskeleton protein vimentin, an emerging target
related to tumor metastasis. Herein, we design a binding-induced fibrillogenesis
(BIF) peptide that in situ forms fibrous networks, blocking the improper
self-assembly of vimentin against cancer. The BIF peptide can bind
to vimentin and subsequently perform fibrillogenesis to form fibers
on vimentin. The resultant peptide fibrous network blocks vimentin
skeletonization and inhibits the migration and invasion of tumor cells.
In mouse models of tumor metastasis, the volume of tumor and the number
of lung metastases are markedly decreased. Moreover, the efficacy
of BIF peptide (5 mg/kg) is much higher than small molecular antimetastasis
drug withaferin A (5 mg/kg) as a standard, indicating that the BIF
peptide shows advantages over small molecular inhibitors in blocking
the intracellular protein self-assembly.
Uncontrolled hemorrhage is a major problem both in surgical intervention and after trauma. Herein, we design an in situ constructable peptide network, mimicking and participating native coagulation process for enhanced...
Allergic
rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin
E (IgE) mediators after individual contact with allergens. It affects
10–40% of the world’s population and reduces the quality
of life. Long-term symptoms of rhinitis can cause inflammation to
spread and trigger asthma, which can harm human health. Herein, we
develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide
web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2,
are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2
is able to bind to IgE and transform from nanoparticles into entangled
nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term
trap of IgE to prevent the IgE from binding to mast cells. SPIN-1
or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high
efficiency and reduced symptoms of rhinitis and inflammatory factors,
even better than a first-line clinical drug, cetirizine (10 mg/kg).
For example, the amount of IL-4 released in the AR group (185.5 ±
6.8 pg/mL) is significantly reduced after the treatment with SPIN-1
(70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine
(112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine
group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic
effects (1 week). The SPIN web technique shows the great potential
for blocking IgE binding to mast cells in vivo, attenuating AR or
other allergic reactions.
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