3 research outputs found
Supramolecular Polymers Formed by ABC Miktoarm Star Peptides
We
report here the design and synthesis of an ABC miktoarm star peptide
connecting through a lysine junction a short peptide sequence and
two hydrophobic but immiscible blocks (a hydrocarbon and a fluorocarbon).
The designed molecule can self-assemble into one-dimensional nanostructures
with a great diversity of kinetically evolving morphologies in aqueous
solution, while molecules that contain only one of the two hydrophobic
blocks form structurally similar filaments. We believe the rich assembly
behavior and morphological evolution are a direct reflection of the
molecular frustration present within the filament core as a result
of the incompatibility of the fluorocarbon and hydrocarbon segments.
Our finding opens new opportunities for creating complex supramolecular
polymers through the architecture design of small molecular building
units
Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
One-dimensional nanostructures formed
by self-assembly of small
molecule peptides have been extensively explored for use as biomaterials
in various biomedical contexts. However, unlike individual peptides
that can be designed to be specifically degradable by enzymes/proteases
of interest, their self-assembled nanostructures, particularly those
rich in β-sheets, are generally resistant to enzymatic degradation
because the specific cleavage sites are often embedded inside the
nanostructures. We report here on the rational design of β-sheet
rich supramolecular filaments that can specifically dissociate into
less stable micellar assemblies and monomers upon treatment with matrix
metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment
to an amyloid-derived peptide sequence, we first synthesized an amphiphilic
peptide that can undergo a rapid morphological transition in response
to pH variations. We then used MMP-2 specific peptide substrates as
multivalent cross-linkers to covalently fix the amyloid-like filaments
in the self-assembled state at pH 4.5. Our results show that the cross-linked
filaments are stable at pH 7.5 but gradually break down into much
shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2.
We believe that the reported work presents a new design platform for
the creation of amyloid-like supramolecular filaments responsive to
enzymatic degradation
Gold Nanoantenna-Mediated Photothermal Drug Delivery from Thermosensitive Liposomes in Breast Cancer
In
this work, we demonstrate controlled drug delivery from low-temperature-sensitive
liposomes (LTSLs) mediated by photothermal heating from multibranched
gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells
in vitro. The unique geometry of MGNs enables the generation of mild
hyperthermia (∼42 °C) by converting near-infrared light
to heat and effectively delivering doxorubicin (DOX) from the LTSLs
in breast cancer cells. We confirmed the cellular uptake of MGNs by
using both fluorescence confocal Z-stack imaging and transmission
electron microscopy (TEM) imaging. We performed a cellular viability
assay and live/dead cell fluorescence imaging of the combined therapeutic
effects of MGNs with DOX-loaded LTSLs (DOX-LTSLs) and compared them
with free DOX and DOX-loaded non-temperature-sensitive liposomes (DOX-NTSLs).
Imaging of fluorescent live/dead cell indicators and MTT assay outcomes
both demonstrated significant decreases in cellular viability when
cells were treated with the combination therapy. Because of the high
phase-transition temperature of NTSLs, no drug delivery was observed
from the DOX-NTSLs. Notably, even at a low DOX concentration of 0.5
μg/mL, the combination treatment resulted in a higher (33%)
cell death relative to free DOX (17% cell death). The results of our
work demonstrate that the synergistic therapeutic effect of photothermal
hyperthermia of MGNs with drug delivery from the LTSLs can successfully
eradicate aggressive breast cancer cells with higher efficacy than
free DOX by providing a controlled light-activated approach and minimizing
off-target toxicity