7 research outputs found
One-Pot Synthesis of Redox-Labile Polymer Capsules via Emulsion Droplet-Mediated Precipitation Polymerization
Monodisperse poly(vinylcaprolactam)
(PVCL)-based capsules are prepared
by precipitation polymerization of vinylcaprolactam (VCL) onto dimethyldiethoxysilane
(DMDES) emulsion droplets and removal of the DMDES templates by ethanol.
Polymer chains in the shells can be cross-linked during the polymerization
by disulfide-containing cross-linker <i>N</i>,<i>N</i>′-bis(acryloyl) cystamine, which endows the capsules with
an excellent redox-labile property. Versatility of this technique
to prepare capsules with diverse components is demonstrated by the
copolymerization of methacrylic acid (MAA) and VCL in the shell to
prepare poly(vinylcaprolactam-<i>co</i>-methacrylic acid)
(P(VCL-<i>co</i>-MAA)) capsules. The disulfide-bonded capsules
can degrade efficiently into low molecular weight species (ca. 1200
Da) when the capsules are incubated with 10 mM glutathione (GSH) as
the reducing agent. Delivery of the anticancer drug (doxorubicin,
DOX) was also investigated in the P(VCL-<i>co</i>-MAA) capsules.
The cumulative <i>in vitro</i> release of DOX-loaded capsules
allows a relatively low DOX release at pH 7.4. However, a burst release
(ca. 90% in 6 h) of DOX was observed in the presence of 10 mM GSH.
Cell viability assays show that the P(VCL-<i>co</i>-MAA)
capsules have negligible cytotoxicity to HeLa cancer cells. In comparison,
DOX-loaded P(VCL-<i>co</i>-MAA) capsules cause significant
cell death following internalization. The reported capsules represent
a novel and versatile class of stimuli-responsive carriers for controlled
drug delivery
A Generic Magnetic Microsphere Platform with “Clickable” Ligands for Purification and Immobilization of Targeted Proteins
While
much effort has been made to prepare magnetic microspheres
(MMs) with surface moieties that bind to affinity tags or fusion partners
of interest in the recombinant proteins, it remains a challenge to
develop a generic platform that is capable of incorporating a variety
of capture ligands by a simple chemistry. Herein, we developed core–shell
structured magnetic microspheres with a high magnetic susceptibility
and a low nonspecific protein adsorption. Surface functionalization
of these MMs with azide groups facilitates covalent attachment of
alkynylated ligands on their surfaces by “click” chemistry
and creates a versatile platform for selective purification and immobilization
of recombinant proteins carrying corresponding affinity tags. The
general applicability of the approach was demonstrated in incorporating
four widely used affinity ligands with different reactive groups (−CHO,
−SH, −COOH, and −NH<sub>2</sub>) onto the MMs
platform for purification and immobilization of targeted proteins.
The azide-functionalized MMs would be applicable for a variety of
ligands and substrates that are amenable to alkynylation modification
Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect
Recently, photothermal therapy (PTT)
that utilizes photothermal
conversion (PTC) agents to ablate cancer under near-infrared (NIR)
irradiation has attracted a growing amount of attention because of
its excellent therapeutic efficacy and improved target selectivity.
Therefore, exploring novel PTC agents with an outstanding photothermal
effect is a current research focus. Herein, we reported a polydopamine-coated
magnetic composite particle with an enhanced PTC effect, which was
synthesized simply through coating polydopamine (PDA) on the surface
of magnetic Fe<sub>3</sub>O<sub>4</sub> particles. Compared with magnetic
Fe<sub>3</sub>O<sub>4</sub> particles and PDA nanospheres, the core–shell
nanomaterials exhibited an increased NIR absorption, and thus, an
enhanced photothermal effect was obtained. We demonstrated the <i>in vitro</i> and <i>in vivo</i> effects of the photothermal
therapy using our composite particles and their ability as a contrast
agent in the <i>T</i><sub>2</sub>-weighted magnetic resonance
imaging. These results indicated that the multifunctional composite
particles with enhanced photothermal effect are superior to magnetic
Fe<sub>3</sub>O<sub>4</sub> particles and PDA nanospheres alone
Plant Protein-Directed Synthesis of Luminescent Gold Nanocluster Hybrids for Tumor Imaging
Nowadays,
fluorescence detection has emerged as one of the most frequently used
noninvasive biosensing methods to selectively monitor biological processes
within living systems. Among fluorescent nanoparticles (NPs), gold
nanoclusters (AuNCs) have been intensively studied because of their
intrinsic fluorescence and their endowed biocompatible surface. Herein,
we selected an abundant, low-cost, and sustainable plant protein,
the pea protein isolate (PPI), for its excellent biocompatibility,
biodegradability, and nonallergenic character to be employed as both
a reducing and stabilizing agent to facilely produce AuNCs exhibiting
a strong red fluorescence. Afterward, the formed AuNCs/PPI mixture
was able to self-assemble into NPs (AuNCs/PPI NPs) with the size of
about 100 nm simply through a dialyzing process. Taking advantage
from the protein nature of PPI, AuNCs/PPI NPs demonstrate both excellent
biocompatibility and colloidal stability. Moreover, AuNCs/PPI NPs
showed a great capability when employed as a bioimaging probe for
both in vitro and in vivo imaging. Finally, AuNCs/PPI NPs were coated
with red blood cell (RBC) membranes to improve their blood circulation
property and enhance their tumor enrichment ability to meet the requirement
for practical use. Results convincingly show that such super NPs (RBC-coated
AuNCs/PPI NPs) were able to successfully locate tumor in vivowith
an excellent imaging capability, which provides a new strategy for
bioimaging with fluorescent NPs
Blocking Autophagic Flux Enhances Iron Oxide Nanoparticle Photothermal Therapeutic Efficiency in Cancer Treatment
Autophagy is a conservative
eukaryotic pathway which plays a crucial
role in maintaining cellular homeostasis, and dysfunction of autophagy
is usually associated with pathological conditions. Recently, emerging
reports have stressed that various types of nanomaterials and therapeutic
approaches interfere with cellular autophagy process, which has brought
up concerns to their future biomedical applications. Here, we present
a study elaborating the relationships between autophagy and iron oxide
nanoparticle (IONP)-mediated photothermal therapy in cancer treatment.
Our results reveal that IONP photothermal effect could lead to autophagy
induction in cancerous MCF-7 cells in a laser dose-dependent manner,
and the inhibition of autophagy would enhance the photothermal
cell killing by increasing cell apoptosis. In an MCF-7 xenograft model,
cotreatment of autophagy inhibitor and IONP under laser exposure could
promote the tumor inhibition rate from 43.26 to 68.56%, and the tumor
immunohistochemistry assay of microtubule-associated protein 1-light
chain 3 (LC3) and terminal deoxynucleotidyl transferase-mediated dUTP
nick-end labeling also demonstrate augmentation in both autophagosomes
accumulation and apoptosis in vivo. This work helps us to better understand
the regulation of autophagy during IONP-mediated photothermal therapy
and provides us with a potential combination therapeutic approach
of autophagy modulators and photothermal agents
Fluorescent Carbonaceous Nanodots for Noninvasive Glioma Imaging after Angiopep‑2 Decoration
Fluorescent carbonaceous nanodots
(CDs) have attracted much attention
due to their unique properties. However, their application in noninvasive
imaging of diseased tissues was restricted by the short excitation/emission
wavelengths and the low diseased tissue accumulation efficiency. In
this study, CDs were prepared from glucose and glutamic acid with
a particle size of 4 nm. Obvious emission could be observed at 600
to 700 nm when CDs were excited at around 500 nm. This property enabled
CDs with capacity for deep tissue imaging with low background adsorption.
Angiopep-2, a ligand which could target glioma cells, was anchored
onto CDs after PEGylation. The product, An-PEG-CDs, could target C6
glioma cells with higher intensity than PEGylated CDs (PEG-CDs), and
endosomes were involved in the uptake process. In vivo, An-PEG-CDs
could accumulate in the glioma site at higher intensity, as the glioma/normal
brain ratio for An-PEG-CDs was 1.73. The targeting effect of An-PEG-CDs
was further demonstrated by receptor staining, which showed An-PEG-CDs
colocalized well with the receptors expressed in glioma. In conclusion,
An-PEG-CDs could be successfully used for noninvasive glioma imaging
New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes
Finding
a simple and effective strategy to eliminate tumor metastatic
lymph nodes is highly desired in clinical tumor treatment. Herein,
we reported a Chinese traditional ink (Hu-ink)-based treatment for
photothermal therapy (PTT) of tumor metastatic lymph nodes. By simple
dilution, stable Chinese traditional ink dispersion was obtained,
which presents excellent photothermal effect because of its high absorption
in near-infrared (NIR) region. Meanwhile, as revealed by staining
and photoacoustic imaging, Hu-ink could transfer to nearby lymph nodes
after directly injected into the primary tumors. Under the guidance
of dual-modality mapping, the metastatic sentinel lymph nodes could
be subsequently eliminated by NIR irradiation. The good biocompatibility
of Hu-ink has also been verified by a series of experiments. Therefore,
the Hu-ink-based treatment exhibits great potential for PTT of tumor
metastatic lymph nodes in future clinical practice